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Avian IgY Antibody:
Avian IgY Antibody: In vitro and in vivo. David Carlander, Ph. D. 2002
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine. Acta Universitatis Upsaliensis. Uppsala. 1119:1-53.
Egg Yolk Antibodies for Passive Immunity Jennifer Kovacs-Nolan and Yoshinori Mine; Annual Review of Food Science and Technology 2012 3:163-82
Inflammation, Stress, and Diabetes
Kathryn E. Wellen and Gökhan S. Hotamisligil
Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity. It is now clear that obesity is associated with a state of chronic low-level inflammation. In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes. We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity. We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease.
Psychoneuroimmunology and Inflammation
Psychoneuroimmunology and Psychosomatic Medicine: Back to the Future
Janice K. Kiecolt-Glaser, Ph.D, Lynanne Mcguire, Ph.D, Theodore F. Robles, BS, and Ronald Glaser, Ph.D
Cardiovascular Function and Immune Modulation
Madej A, Okopien B, Kowalski J, Haberka M, Herman ZS Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension. Pharmacol Rep. 2005 Nov-Dec;57(6):878-81. Department of Clinical Pharmacology, Silesian University School of Medicine, Medykow 18, PL 40-752 Katowice, Poland. andrzejmadej@o2.pl.
Arterial hypertension vascular injury results in serious complications, such as left-ventricular hypertrophy and myocardial failure, ischemic heart disease and cerebral stroke. Currently, it is well known that inflammatory factors play a significant role in the mechanisms that trigger and enhance the remodeling of the vascular wall. A number of data suggest an important role of adhesion molecules and chemokines in this processes. The aim of this study was measuring the plasma levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) and Monocyte Chemoattractant Peptide1 (MCP-1) in patients with essential hypertension vs. healthy volunteers by ELISA method (R&D kits). sICAM-1 and MCP-1 levels were significantly higher in hypertensive patients compared to controls (sICAM-1: 279.2 +/- 8.8 ng/ml vs. 224.4 +/- 1.8 ng/ml; p < 0.001; MCP-1: 142.2 +/- 7 pg/ml vs. 95.4 +/- 36 pg/ml; p < 0.0001. Our results indicate that arterial hypertension alone (without inflammation, lipid and carbohydrate disorders) may increase the expression of these cytokines and contribute to the progression of endothelial injury.
Antelava N, Pachkoria K, Kezeli T, Nikuradze N, Shamkulashvili G. [Major pathogenic links of atherosclerosis.] [ Article in Russian ] Georgian Med News. 2005 128:72-9. Georgian Med News. 2005 Nov;(128):72-9. [Major pathogenic links of atherosclerosis.] [Article in Russian] Antelava N, Pachkoria K, Kezeli T, Nikuradze N, Shamkulashvili G. Tbilisi State Medical University .
The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, remodulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases.
Casteilla L, Planat-Benard V, Cousin B, Silvestre JS, Laharrague P, Charriere G,Carriere A, Penicaud L. Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases? Arch Mal Coeur Vaiss. 2005 Sep;98(9):922-6. UMR 5018 CNRS UPS, Institut Louis Bugnard, Toulouse, France.
The adipose tissue represents a large amount of adult tissues. For long time, it was considered as a poorly active overgrown and undesirable tissue even if its usefulness was demonstrated in reconstructive surgery. It was studied for its main involvement in energy metabolism and disorders as diabetes and obesity. More recently, its endocrine functions emerged and appeared to play a key role in many physiological situations such as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. These cells can display a macrophagic or endothelial potential according to their environment and could be now considered as vascular progenitors. Differentiation of various adipose derived cell subsets towards functional cardiomyocytes, osteoblasts, haematopoietic and neural cells was also obtained in vitro. Altogether, these data emphasise the need to consider with a new look preadipocyte status and adipose tissue biology. These spectacular data, together with the fact that adipose tissue is easy to obtain lead to numerous and promising perspectives in regenerative medicine. They highlight the concept that progenitor cells from adipose tissue constitute an alternative for cells-based strategies designed for the treatment of cardiovascular diseases.
Bacon PA, Raza K, Banks MJ, Townend J, Kitas GD
The role of endothelial cell dysfunction in the cardiovascular mortality of RA.
Int Rev Immunol 2002 21:1-17
Brasier AR, Recinos A 3rd, Eledrisi MS.
Vascular inflammation and the renin-angiotensin system.
Arterioscler Thromb Vasc Biol 2002 2 22:1257-66
Ferreira MB, Carlos AG.
Heat-shock proteins and atherosclerosis.
Allerg Immunol (Paris) 2002 34:204-207
Hansson GK, Libby P, Schonbeck U, Yan ZQ
Innate and adaptive immunity in the pathogenesis of atherosclerosis.
Circ Res 2002 91:281-91
Exercise and Immune System Function
Wolfel EE. Marathoners or couch potatoes: what is the role of exercise in the management of heart failure? Curr Heart Fail Rep. 2005 Mar;2(1):25-34. Division of Cardiology, B-130, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA . gene.wolfel@uchsc.edu
Patients with chronic heart failure have diminished exercise capacity as a major aspect of their clinical syndrome, regardless of the cause of their left ventricular contractile dysfunction. The mechanisms for the reduction in exercise capacity are multifactorial and include central cardiac, peripheral vascular, respiratory, and skeletal muscle maladaptations that accompany the pathophysiology of heart failure. Increased sympathetic nervous system activity and elevations in circulating neurohormones and cytokines also influence the cardiovascular and metabolic responses to exercise in these patients. Despite the improvements in clinical outcomes with beta-blockers and resynchronization therapy in heart failure patients, their exercise capacity remains substantially reduced when compared with normal age-matched patients. Exercise training has the potential to reverse or improve most of the abnormal physiologic responses to exercise in these patients, and it may serve as adjunctive therapy to standard medical care of these patients. In addition, a body of evidence is being accumulated that suggests that exercise training itself has important secondary prevention benefit in these patients. This review identifies the potential mechanisms whereby exercise training may improve exercise capacity in patients with chronic heart failure and presents the current informationregarding clinical outcomes of this therapy.
Berggren JR, Hulver MW, Houmard JA. Fat as an endocrine organ: influence of exercise. J Appl Physiol. 2005 Aug;99(2):757-64. Human Performance Laboratory and Department of Exercise and Sport Science, 363 Ward Sports Medicine Bldg., East Carolina University, Greenville, NC 27858, USA. berggrenj@mail.ecu.edu
The prevalence of diabetes and obesity continues to increase. It is therefore important to identify the pathophysiology underlying these disorders. An inability of insulin to stimulate glucose uptake, i.e., insulin resistance, appears to be a common link between diabetes and obesity. The identification of various adipocyte-secreted cytokines (adipocytokines) that influence satiety, energy balance, and insulin sensitivity provide a novel target for the treatment of these disorders. Adipocytokines are differentially expressed with obesity and diabetes, making them a strong candidate for linking insulin resistance to these pathological conditions. This review explores the role of adipocytokines in insulin action and examines the effect of exercise training on adipocytokine content.
Febbraio MA, Pedersen BK. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exerc Sport Sci Rev. 2005 Jul;33(3):114-9. Cellular and Molecular Metabolism Laboratory, RMIT University, Bundoora, Australia.
The concentration of plasma interleukin-6 (IL-6) increases during physical exercise, but until recently the cellular origin of this increase has been unknown. Recent work has identified that skeletal muscle is a major source of this increase and the release of IL-6 from muscle can mediate metabolic processes. IL-6 is, therefore, the first identified "myokine" released from muscle that can now be termed an endocrine organ.
Bishop NC; Blannin AK; Walsh NP; Robson PJ; Gleeson M. Nutritional Aspects of Immunosuppression in Athletes. Sport Med 1999 Sep; 28 (3): 151 - 176.
Evans CH. Cytokines and the Role They Play in the Healing of Ligaments and Tendons. Sport Med 1999 Aug; 28 (2): 71-76.
Friman G; Wesslen L. Special Feature for the Olympics: effects of exercise on the immune system: infections and exercise in high performance athletes. Immunology & Cell Biology 2000 Oct; 78 (5): 510-522.
Gleeson, M; Lancaster GI; Bishop, NC. Nutritional strategies to minimize exercise induced immunosuppression in athletes. Can J Appl Physiol 2001; 26 Suppl: S23-35.
Gleeson M; Bishop NC. Special feature of the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate and anti-oxidant supplements. Immunology & Cell Biology 2000 Oct; 78(5): 554-61.
Gleeson M. Special feature of the Olympics: effects of exercise on the immune system. Overview: exercise immunology. Immunology & Cell Biology 2000 Oct;78(5):483-4.
Gleeson M.; Pyne DB. Special feature of the Olympics: effects of exercise on the immune system: exercise effects on mucosal immunity. Immunology & Cell Biology 200 Oct; 78(5):536-44.
Jonsdottir IH. Special feature of the Olympics: effects of exercise on the immune system: Neuropeptides and their interaction with exercise and immune function. Immunology & Cell Biology 200 Oct; 78 (5): 562 - 570.
Konig D; Weinstock C; Keul J; Northoff H; Berg A. Zinc, iron and magnesium status in athletes - influence on the regulation of exercise-induced stress and immune function. Exer Immunol. Review 1998; 4: 2-21.
Malm C; Lenkei R; Sjodin B. Effects of eccentric exercise on the immune system in men. J Appl Physiol 1999 Feb;86(2):461-8
Nieman DC. Special feature of the Olympics: effects of exercise on the immune system: exercise effects on systemic immunity. Immunology & Cell Biology 2000 Oct; 78(5):496-501.
Nieman DC; Pedersen BK. Exercise and immune function: Recent developments. Sports Med 1999 Feb; 27(2): 73-80.
O'Kennedy R. The immune system in sport: getting the balance right. Br J Sports Med 2000 Jun; 34 (3): 161.
Pedersen BK. Special feature of the Olympics: Effects of exercise on the immune system. Exercise and cytokines. Immunology & Cell Biology 2000 Oct: 78(5) 532.
Pedersen BK; Hoffman-Goetz L. Exercise and the immune system: regulation integration, and adaptation. Physiol Review 2000 Jul; 80(3):1055-81.
Pedersen BK; Bruunsgaard H; Jensen M; Toft AD; Hasen H; Ostrowski K. Exercise and the immune system- influence of nutrition and ageing. J Sci Med Sport 1999 Oct; 2 (3): 234-52.
Shephard RJ. Special feature of the Olympics: effects of exercise on the immune system: overview of the epidemiology of exercise immunology. Immunology & Cell Biology 2000 Oct; 78(5):485-95.
Shephard RJ; Slick PN. Effects of Exercise and Training on Natural Killer Cell Counts and Cytolytic Activity. Sports Med 1999 Sep; 28 (3): 177-195.
Simonson SR. The immune response to resistive exercise. J Strength & Conditioning Research 2001 Aug;15(3):378-84.
Speich M; Pineau A; Bllerreau F. Minerals, trace elements and related biological variables in athletes and during physical activity. Clin Chim Acta 2001 Oct; 312(1-2): 1-11.
Venkatraman JT; Peddergast DR. Effect of dietary intake on immune function in athletes. Sports Med 2002; 32(5):323-37.
Woods JA; Lu Q; Ceddia MA; Lowder T. Special feature of the Olympics: effects of exercise on the immune system: exercise induced modulation of macrophage function. Immunology & Cell Biology 2000 Oct: 78 (5): 545 - 553.
Gastrointestinal Function
Sollid LM, Khosla C. Future therapeutic options for celiac disease. Nat Clin Pract Gastroenterol Hepatol. 2005 Mar;2(3):140-7. University of Oslo and Rikshopitalet University Hospital, Norway. l.m.sollid@medisin.uio.no
Celiac disease is a disorder of the small intestine caused by an inappropriate immune response to wheat gluten and similar proteins of barley and rye. At present, the only available treatment is a strict gluten-exclusion diet; hence the need for alternative treatments. Recent advances have improved our understanding of the molecular basis for this disorder and there are several attractive targets for new treatments. Oral enzyme supplementation is designed to accelerate gastrointestinal degradation of proline-rich gluten, especially its proteolytically stable antigenic peptides. Complementary strategies aiming to interfere with activation of gluten-reactive T cells include the inhibition of intestinal tissue transglutaminase activity to prevent selective deamidation of gluten peptides, and blocking the binding of gluten peptides to the HLA-DQ2 or HLA-DQ8 molecules. Other possible treatments include cytokine therapy, and selective adhesion molecule inhibitors that interfere with inflammatory reactions, some of which are already showing promise in the clinic for other gastrointestinal diseases.
Atreya R, Neurath MF. Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer. Clin Rev Allergy Immunol. 2005 Jun;28(3):187-96. Laboratory of Immunology, I. Medical Clinic, University of Mainz, 55131 Mainz, Germany . neurath@1-med.klinik.unimainz.de
Inflammatory bowel disease (IBD), which consists of Crohn's disease and ulcerative colitis, is defined as a chronic inflammation of the gastrointestinal tract. The etiopathogenetic mechanisms underlying the development of IBD are still not completely understood, and the therapeutic strategies used thus far have been limited to mostly evidence-based principles. There is growing evidence that the pro-inflammatory cytokine interleukin (IL)-6 plays a crucial part in the uncontrolled intestinal inflammatory process, which is a main characteristic of IBD. There is elevated production of IL-6 and its soluble receptor (sIL-6R) by intestinal macrophages and CD4+T-cells. The increased formation of IL-6-sIL-6R complexes that interact with gp130 on the membrane of CD4+T-cells (trans-signaling) lead to an increased expression and nuclear translocation of STAT3, which causes the induction of anti-apoptotic genes, such as Bcl-xl. This leads to an augmented resistance of lamina propria T-cells to apoptosis. The ensuing T-cell expansion contributes to the perpetuation of chronic intestinal inflammation. This understanding concerning the predominant pathogenic role of an IL-6-dependent inflammatory cascade may lead to the development of new therapeutic strategies in the treatment of this disease. Recent studies have also suggested a potential role of IL-6-sIL-6R in the pathogenesis of colon cancer and, therefore, imply a possible novel therapeutic strategy targeting the sIL-6R and ensuing IL-6 trans-signaling.
Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci. 2005 Oct;50 Suppl 1:S24-33. Department of Medicine, VA Long Beach Healthcare System Long Beach, Long Beach, California 90822, USA . atarnawski@yahoo.com
This paper reviews cellular and molecular mechanisms of gastrointestinal ulcer healing. Ulcer healing, a genetically programmed repair process, includes inflammation, cell proliferation, re-epithelialization, formation of granulation tissue, angiogenesis, interactions between various cells and the matrix and tissue remodeling, all resulting in scar formation. All these events are controlled by the cytokines and growth factors (EGF, PDGF, KGF, HGF, TGFbeta, VEGF, angiopoietins) and transcription factors activated by tissue injury in spatially and temporally coordinated manner. These growth factors trigger mitogenic, motogenic and survival pathways utilizing Ras, MAPK, PI-3K/Akt, PLC-gamma and Rho/Rac/actin signaling. Hypoxia activates pro-angiogenic genes (e.g., VEGF, angiopoietins) via HIF, while serum response factor (SRF) is critical for VEGF-induced angiogenesis, re-epithelialization and muscle restoration. EGF, its receptor, HGF and Cox2 are important for epithelial cell proliferation, migration re-epithelializaton and reconstruction of gastric glands. VEGF, angiopoietins, nitric oxide, endothelin and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within ulcer scar. Circulating progenitor cells are also important for ulcer healing. Local gene therapy with VEGF + Ang1 and/or SRF cDNAs dramatically accelerates esophageal and gastric ulcer healing and improves quality of mucosal restoration within ulcer scar. Future directions to accelerate and improve healing include the use of stem cells and tissue engineering.
Aithal GP, Craggs A, Day CP, Welfare M, Daly AK, Mansfield JC, Hudson M.
Role of Polymorphisms in the Interleukin-10 Gene in Determining Disease Susceptibility and Phenotype in Inflamatory Bowel Disease.
Dig Dis Sci 200146:1520-5
Caprilli R, Viscido A, Guagnozzi D.
Biological Agents in theTreatment of Crohn's Disease.
Aliment Pharmacol Ther 2002 16:1579-90
Forsberg G, Hernell O, Melgar S, Israelsson A, Hammarstrom S, Hammarstrom ML.
Paradoxical Coexpression of Proinflammatory and Down-Regulatory Cytokines in Intestinal T cells in Childhood Celiac Disease.
Gastroenterology 2002 123:667-78
Katsuta T, Lim C, Shimoda K, Shibuta K, Mitra P, Banner BF, Mori M, Barnard GF.
Interleukin-8 and SDF1-alpha mRNA Expression in Colonic Biopsies from Patients with inflammatory Bowel Disease.
Am J Gastroenterol 2000 95:3157-64
Podolsky DK.
Inflammatory Bowel Disease.
N Engl J Med 2002 347:417-29
Immunological Regulation
Connolly NC, Riddler SA, Rinaldo CR. Proinflammatory cytokines in HIV disease-a review and rationale for new therapeutic approaches. AIDS Rev. 2005 Jul-Sep;7(3):168-80. University of Pittsburgh, Pittsburgh, PA 15213, USA. connollync@dom.pitt.edu
Antiretroviral drugs currently in use for treating HIV-1 infection are very effective at maintaining low viral loads and clinical stability, but have been limited by their inability to eradicate virus in infected individuals, resulting in the need for indefinite therapy. The inability of antiretroviral drug therapy to eliminate HIV-1 infection is thought to be due to incomplete restoration of host immunity to the virus. New strategies to improve control of HIV-1 infection during antiretroviral therapy should target enhancement of host immunity. Proinflammatory cytokines are the central mediators of both innate and adaptive immunity, and modulation of these cytokines has been shown to alter anti-HIV-1 reactivity in vitro. Modulation of proinflammatory cytokines could therefore be utilized in strategies for immunotherapy of HIV-1 infection. The ultimate goal is to find regimens that could more durably suppress viral replication and potentially eliminate the need for indefinite antiretroviral therapy. This review presents what is known about the dysregulation of proinflammatory cytokines in HIV-1 infection, highlighting newly available immune-based therapies that could augment antiretroviral drug therapies.
Nelson RB. The dualistic nature of immune modulation in Alzheimer's disease: lessons from the transgenic models. Curr Pharm Des. 2005;11(26):3335-52. Pfizer Global R&D, Groton Laboratories, Neuroscience Discovery, MS 8220-4015, Eastern Point Road, Groton, CT 06340, USA. robert.b.nelson@ pfizer.com
There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimer's disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, and the difficulty in identifying the key molecular players that underlie any given immunological response, expanding our understanding of the immunological response in AD beyond its descriptive stages has not been a straightforward exercise. The development of transgenic animals that form deposits of Abeta peptide in their brains has provided an unexpected dividend to those interested in the immunological response characterizing AD. Several of these transgenic models develop structures greatly resembling neuritic plaques, a hallmark feature of AD brain that is also a focal point of the immunological response occurring in AD. Genetic and pharmacological manipulation of these Abeta-depositing transgenic mice is providing some intriguing and unexpected insights into the role of innate and adaptive immune mechanisms in the pathogenesis of AD. This review will discuss immunological perspectives that have arisen from research using Abeta-depositing transgenic mice, and place these perspectives in the context of epidemiological and genetic studies that have previously suggested a role for the immune system in AD. The emerging story affirms the likely role of innate and adaptive immune mechanisms in the pathogenesis of AD, but provides a cautionary note as to the difficulties that are likely to face potential immunomodulatory therapies due to the dualistic beneficial and detrimental roles that immune mechanisms appear to play in AD.
Esper DH, Harb WA. The cancer cachexia syndrome: a review of metabolic and clinical manifestations. Nutr Clin Pract. 2005 Aug;20(4):369-76. Horizon Oncology, Lafayette, Indiana, USA. dhalasa_esper@yahoo.com
The progressive deterioration in nutrition status frequently seen in cancer patients is often referred to as cancer cachexia. Unlike starvation, in which fat stores from adipose are depleted and protein is spared from skeletal muscle, neither fat nor protein is spared in cachexia. Cachexia affects nearly half of cancer patients, causing the clinical manifestations of anorexia, muscle wasting, weight loss, early satiety, fatigue, and impaired immune response. Cachexia does not only impede the response to chemotherapy but also is a major cause of morbidity and mortality. According to clinical studies, increasing caloric intake does not necessarily reverse cachexia. The pathophysiology of cachexia involves more complex mechanisms than simply caloric deficiency. The process appears to be mediated by circulating catabolic factors, either secreted by the tumor alone or in concert with host-derived factors, such as tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1 and IL-6), interferon (IFN-y), and leukemia inhibitory factor (LIF). The successful reversal of this process will require in-depth knowledge of the mechanisms involved, which will then enable the development of effective pharmacologic interventions that may not only improve quality of life, but more importantly, improve survival among cancer patients.
Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005 Nov 12;366(9498):1736-43. Department of Dermatology, Boston University, Boston, MA, USA. vfalanga@bu.edu
Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.
Carlstedt, Fredrik: Calcium metabolism and cytokines in critical illness. - Uppsala Doctoral Dissertation, 1998.
Clauw DJ
Potential Mechanisms in Chemical Intolerance and Related Conditions
Ann NY Acad Sci 2001 933: 235-253.
.
Dantzer R.
Cytokine-Induced Sickness Behavior: Mechanisms and Implications
Ann NY Acad Sci 2001 933: 222-234.
Infection and Immune Modulation
Connolly NC, Riddler SA, Rinaldo CR. Proinflammatory cytokines in HIV disease-a review and rationale for newtherapeutic approaches. AIDS Rev. 2005 Jul-Sep;7(3):168-80. University of Pittsburgh, Pittsburgh, PA 15213, USA. connollync@dom.pitt.edu
Antiretroviral drugs currently in use for treating HIV-1 infection are very effective at maintaining low viral loads and clinical stability, but have been limited by their inability to eradicate virus in infected individuals, resulting in the need for indefinite therapy. The inability of antiretroviral drug therapy to eliminate HIV-1 infection is thought to be due to incomplete restoration of host immunity to the virus. New strategies to improve control of HIV-1 infection during antiretroviral therapy should target enhancement of host immunity. Proinflammatory cytokines are the central mediators of both innate and adaptive immunity, and modulation of these cytokines has been shown to alter anti-HIV-1 reactivity in vitro. Modulation of proinflammatory cytokines could therefore be utilized in strategies for immunotherapy of HIV-1 infection. The ultimate goal is to find regimens that could more durably suppress viral replication and potentially eliminate the need for indefinite antiretroviral therapy. This review presents what is known about the dysregulation of proinflammatory cytokines in HIV-1 infection, highlighting newly available immune-based therapies that could augment antiretroviral drug therapies.
Chatila TA. Role of regulatory T cells in human diseases. J Allergy Clin Immunol. 2005 Nov;116(5):949-59; quiz 960. Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, The David Geffen School of Medicine at the University of California at Los Angeles, USA . tchatila@mednet.ucla.net
The discovery of regulatory T lymphocytes (Treg) that are actively involved in maintaining immune tolerance has led to new insights into mechanisms of tolerance breakdown in human diseases, including those resulting from allergic, autoimmune, or infectious causes. Congenital deficiency of CD4(+)CD25(+) Treg cells caused by loss-of-function mutations in the gene encoding Foxp3 triggers a syndrome of lymphoproliferation and myeloproliferation, autoimmunity, and allergic dysregulation, whereas deficient allergen-specific Treg cell responses have been associated with a number of allergic and autoimmune disorders. Tolerization to allergens and autoantigens is associated with augmentation of Treg cell numbers and suppressive function, suggesting the manipulation of Treg cell activity as a potential strategy for future therapeutic interventions in allergic and autoimmune diseases.
Dongari-Bagtzoglou A, Fidel PL Jr. The host cytokine responses and protective immunity in oropharyngealcandidiasis. Dent Res. 2005 Nov;84(11):966-77. School of Dental Medicine, Department of Oral Health and Diagnostic Sciences, University of Connecticut, 263 Farmington Ave., Farmington, CT 06030-1710, USA. adongari@uchc.edu
Over the last three decades, the prevalence of oropharyngeal fungal infections has increased enormously, mainly due to an increasing population of immunocompromised patients, including individuals with HIV infection, transplant recipients, and patients receiving cancer therapy. The vast majority of these infections are caused by Candida species. The presence of cytokines in infectedtissues ultimately dictates the host defense processes that are specific to each pathogenic organism. During oral infection with Candida, a large number of pro-inflammatory and immunoregulatory cytokines are generated in the oral mucosa. The main sources of these cytokines are oral epithelial cells, which maintain a central role in the protection against fungal organisms. These cytokines may drive the chemotaxis and effector functions of innate and/or adaptive effector cells, such as infiltrating neutrophils and T-cells in immunocompetent hosts, and CD8(+) T-cells in HIV(+) hosts. Epithelial cells also have direct anti-Candida activity. Several studies have provided a potential link between lower levels of certain pro-inflammatory cytokines and susceptibility to oral C. albicans infection, suggesting that such cytokines may be involved in immune protection. The exact role of these cytokines in immune protection against oropharyngeal candidiasis is still incompletely understood and requires further investigation. Identification of such cytokines with the ability to enhance anti-fungal activities of immune effector cells may have therapeutic implications in the treatment of this oral infection in the severely immunocompromised host.
Chen YC, Wang SY.
Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide.
J Virol 2002 76:9877-87
Jenkinson L, Bardhan KD, Atherton J, Kalia N.
Helicobacter pylori prevents proliferative stage of angiogenesis in vitro: role of cytokines.
Dig Dis Sci 2002 47:1857-62
Lean IS, McDonald V, Pollok RC
The role of cytokines in the pathogenesis of Cryptosporidium infection.
Curr Opin Infect Dis 2002 15:229-34
Nedrud JG, Blanchard SS, Czinn SJ.
Helicobacter pylori inflammation and immunity.
Helicobacter 2002 Suppl 1:24-9
Sanclemente G, Gill DK.
Human papillomavirus molecular biology and pathogenesis.
J Eur Acad Dermatol Venereol 2001 16:231-40
Inflammation and Immune Modulation
Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathicosteoarthropathy (acute Charcot foot) in diabetes. Lancet. 2005 Dec 10;366(9502):2058-61. Epub 2005 Aug 10. Foot Ulcer Trials Unit, Department of Diabetes and Endocrinology, City Hospital, Nottingham NG5 1PB, UK . wjeffcoate@futu.co.uk
The pathogenesis of the acute Charcot foot of diabetes remains unclear. All patients with this condition have evidence of peripheral neuropathy, with loss of protective sensation and abnormal foot biomechanics. However, the acute Charcot foot is also characterised by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. We suggest that an initial insult--which may or may not be detected--is sufficient to trigger an inflammatory cascade through increased expression of proinflammatory cytokines, including TNFalpha and interleukin 1beta. This cascade then leads to increased expression of the nuclear transcription factor, NF-kappaB, which results in increased osteoclastogenesis. Osteoclasts cause progressive bone lysis, leading to further fracture, which in turn potentiates the inflammatory process. The potential role of proinflammatory cytokines suggests the possibility of new treatments for this sometimes devastating complication of diabetes.
Moss SF, Blaser MJ Mechanisms of disease: Inflammation and the origins of cancer. Nat Clin Pract Oncol. 2005 Feb;2(2):90-7; quiz 1 p following 113. Rhode Island Hospital and Department of Medicine, Brown University, Providence, Rhode Island 02903, USA. Steven_Moss@brown.edu
Many common cancers develop as a consequence of years of chronic inflammation. Increasing evidence indicates that the inflammation may result from persistent mucosal or epithelial cell colonization by microorganisms; including hepatitis B virus and hepatitis C virus, which can cause hepatocellular cancer; human papilloma virus subtypes, which cause cervical cancer, and the bacterium Helicobacter pylori, which can cause gastric cancer. At present, the cause of other chronic inflammatory conditions associated with increased cancer risk, such as ulcerative colitis, is obscure. Particular microbial characteristics as well as the type of the inflammatory response contribute to clinical outcomes via influence on epithelial cell and immune responses. Persistent inflammation leads to increased cellular turnover, especially in the epithelium, and provides selection pressure that result in the emergence of cells that are at high risk for malignant transformation. Cytokines, chemokines, free radicals, and growth factors modulate microbial populations that colonize the host. Thus, therapeutic opportunities exist to target the causative microbe, the consequent inflammatory mediator, or epithelial cell responses. Such measures could be of value to reduce cancer risk in inflammation-associated malignancies.
Liu G, Rondinone CM. JNK: bridging the insulin signaling and inflammatory pathway. Curr Opin Investig Drugs. 2005 Oct;6(10):979-87. Abbott Laboratories, Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA.
Obesity and insulin resistance are strongly associated with systemic markers of inflammation and endoplasmic reticulum stress. c-Jun N-terminal kinases (JNK) are activated by inflammatory cytokines and have a key role in beta-cell apoptosis and in negative regulation of insulin signaling. JNK1-deficient mice are protected from diet-induced obesity and insulin resistance, while genetically obese mice with targeted mutations in JNK1 are leaner and have reduced insulin and blood glucose levels. These studies validate JNK as a link between inflammation and metabolic diseases and as a promising drug target. This review highlights recent advances in small-molecule inhibitors of JNK that have also been targeted for other diseases with an inflammatory component such as stroke, rheumatoid arthritis, and Alzheimer's and Parkinson's diseases.
Agostini C, Meneghin A, Semenzato G
T-lymphocytes and Cytokines in Sarcoidosis.
Curr Opin Pulm Med 2002 8:435-40
Ajuebor MN, Swain MG, Perretti M.
Chemokines as Novel Therapeutic Targets in Inflammatory Diseases.
Biochem Pharmacol 2002 63:1191-6
Luzzi GA.
Chronic Prostatitis and Chronic Pelvic Pain in Men: Aetiology, Diagnosis and Management.
J Eur Acad Dermatol Venereol 2001 16:253-6
Joints, Bones and Immune Modulation
Williams RO, Inglis JJ, Simelyte E, Criado G, Sumariwalla PF. Analysing the effect of novel therapies on cytokine expression in experimental arthritis. Int J Exp Pathol. 2005 Oct;86(5):267-78. Kennedy Institute of Rheumatology Division, Imperial College London, London, UK. richard.o.williams@imperial.ac.uk
Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro-inflammatory cytokines, such as tumour necrosis factor alpha and interleukin-1beta, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small-molecular-weight inhibitors of pro-inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention.
Schacht E. [Present and future therapeutic strategies in rheumatoid arthritis] [Article in German] Z Rheumatol. 1993 52:365-82 E. Tosse & Co. GmbH, Hamburg. Z Rheumatol. 1993 Nov-Dec;52(6):365-82.
The triad of inflammation, immunoproliferation and synovial hyperplasia is recognized in the pathogenesis of rheumatoid arthritis, however, the sequence of events remains as highly controversial as ever. The "RA pyramid" was established on the assumption that inflammation is at the top with the destructive processes as sequelae. The moderate successes achieved by conservative therapy with regard to long-term outcome cast doubt on this hypothesis. Inhibitors of prostaglandin synthesis have not been and are not disease modifying. Do substances which influence the endothelial adhesion molecules or leucocyte adhesion receptors (leumedines) promise to be more successful? Do the empirically developed disease modifying antirheumatic drugs (Gold parenteral, MTX) have to be administered earlier? Unfortunately, there is a need for a differential diagnosis which is prognostically valid with regard to the dynamics and aggressiveness of rheumatoid arthritis. Moreover, a pharmacological basis for optimally founded combination strategies is also lacking. Presently, the emphasis of research is directed at the regulation of dysfunctional immune systems. Immunosuppressives (cyclosporin A), cytokine antagonists, receptor antagonists and soluble cytokine receptors (IL-1, IL-6, TNF-alpha), antibodies against lymphocyte subgroups (CD4, CD7) or against cytokines and their receptors are part of the arsenal for the medium term. Too little is still known about the role of protective cytokines (TGF-beta, IL-4, gamma-INF). Currently, however, it is prognosticated that these targeted therapies will only succeed in RA subgroups or only in intelligent combinations. More attractive alternative are strategic therapy modalities which intervene very early in the pathological process, such as the modulation of antigen presentation (MHC blocking peptides, T-cell receptor antagonists, T-cell vaccination) or the induction of tolerance against autoantigens through the oral administration of antigens (collagen II, HSP's, OM-8980). If the center of the pathological process, however, is found in the synovial proliferation of tumor-like cell clusters, then there are only a few years at the beginning of the disease when there is a real chance to impede destruction. In this case, aggressive induction therapy can be the only key to success. In the future, specifically active cytostatics (inhibitors of angiogenesis) will have to be developed and clinical trials conducted on adjuvant therapies with substances which strengthen bone and cartilage, making them more resistant to aggressive cell clusters (bisphosphonates, calcitonins, metalloproteinase- or collagenase-inhibitors).
Takeuchi T. [Biological agents targeting on pro-inflammatory cytokines] [Article in Japanese] Nippon Rinsho. 2005 Sep;63(9):1601-6. Department of Rheumatology/Clinical Immunology, Saitama Medical Center.
Biological agents targeting on pro-inflammatory cytokines are developed, and provide a great impact on the medical management of rheumatoid arthritis (RA). Particularly, biologics against tumor necrosis factor(TNF) can not only induce great clinical improvement, but also halt structural damage on the joints. Now chimeric anti-TNFalpha monoclonal antibody, infliximab, full human anti-TNFalpha monoclonal antibody, adalimumab, and TNF receptor II (p75) -IgGFc fusion protein, etanercept, are widely used in the inflammatory disorders including RA. This review article shows the characteristics of these anti-TNF biologics on RA, and summarizes the efficacy as well as the safety of the agents.
Bornefalk, Eva: Cytokines and bone : On the role of IL-1 and IL-6 in bone metabolism. - Uppsala Doctoral Dissertation 1998.
Cassim B, Mody G, Bhoola K.
Kallikrein cascade and cytokines in inflamed joints.
Pharmacol Ther 2002 94:1-34
Gerli R, Bistoni O, Russano A, Fiorucci S, Borgato L, Cesarotti ME, Lunardi C.
In vivo activated T cells in rheumatoid synovitis. Analysis of Th1- and Th2-type cytokine production at clonal level in different stages of disease.
Clin Exp Immunol 2002 129:549-55
van Roon JA, Bijlsma JW, Lafeber FP
Suppression of inflammation and joint destruction in rheumatoid arthritis may require a concerted action of Th2 cytokines.
Curr Opin Investig Drugs 2002 3:1011-6
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Expression of interleukin-1 beta, tumor necrosis factor alpha, interleukins-6, -10 and -4, and metalloproteases by freshly isolated mononuclear cells from early never-treated and non-acute treated rheumatoid arthritis patients.
Clin Exp Rheumatol 1999 17:575-83
Walsmith J, Roubenoff R.
Cachexia in rheumatoid arthritis.
Int J Cardiol 2002 85:89-99
Nervous System Function and Immune Modulation
Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005 Nov 5;366(9497):1653-66. Department of Clinical Neuroscience, King's College London School of Medicine, Guy's Hospital, UK. richard.a.hughes@kcl.ac.uk
Guillain-Barre syndrome consists of at least four subtypes of acute peripheral neuropathy. Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain-Barre syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain-Barre syndrome have had a recent Campylobacter jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy. Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy. The Fisher's syndrome subtype is especially associated with antibodies to GQ1b, and similar cross-reactivity with ganglioside structures in the wall of C jejuni has been discovered. Anti-GQ1b antibodies have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism. Results of international randomised trials have shown equivalent efficacy of both plasma exchange and intravenous immunoglobulin, but not corticosteroids, in hastening recovery from Guillain-Barre syndrome. Further research is needed to discover treatments to prevent 20% of patients from being left with persistent and significant disability.
Shepherd AJ, Downing JE, Miyan JA. Without nerves, immunology remains incomplete -in vivo veritas. Immunology. 2005 Oct;116(2):145-63. Faculty of Life Sciences, The University of Manchester, Manchester, UK.
Interest in the interactions between nervous and immune systems involved in both pathological and homeostatic mechanisms of host defence has prompted studies of neuroendocrine immune modulation and cytokine involvement in neuropathologies. In this review we concentrate on a distinct area of homeostatic control of both normal and abnormal host defence activity involving the network of peripheral c-fibre nerve fibres. These nerve fibres have long been recognized by dermatologists and gastroenterologists as key players in abnormal inflammatory processes, such as dermatitis and eczema. However, the involvement of nerves can all too easily be regarded as that of isolated elements in a local phenomenon. On the contrary, it is becoming increasingly clear that neural monitoring of host defence activities takes place, and that involvement of central/spinal mechanisms are crucial in the co-ordination of the adaptive response to host challenge. We describe studies demonstrating neural control of host defence and use the specific examples of bone marrow haemopoiesis and contact sensitivity to highlight the role of direct nerve fibre connections in these activities. We propose a host monitoring system that requires interaction between specialized immune cells and nerve fibres distributed throughout the body and that gives rise to both neural and immune memories of prior challenge. While immunological mechanisms alone may be sufficient for local responsiveness to subsequent challenge, data are discussed that implicate the neural memory in co-ordination of host defence across the body, at distinct sites not served by the same nerve fibres, consistent with central nervous mediation.
Nagatsu T, Sawada M. Inflammatory process in Parkinson's disease: role for cytokines. Curr Pharm Des. 2005;11(8):999-1016. Fujita Health University , Institute for Comprehensive Medical Science, Toyoake, Aichi, 470-1192, Japan. tnagatsu@fujita-hu.ac.jp
Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the nigrostriatal region of postmortem brains and/or in the ventricular or lumbar cerebrospinal fluid (CSF) from patients with sporadic PD, and in animal models, such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)- and 6-hydroxydopamine (6-OHDA)-induced PD. These changes in cytokine and neurotrophin levels may be initiated by activated microglia, which may then promote apoptotic cell death and subsequent phagocytosis of DA neurons. Cytokines as pleiotropic factors, promote signals that either lead to cell death or exert neuroprotective effects. The discovery of toxic changes in trophic microglia by M. Sawada and co-workers is important to this point. Ultimately, microglial cells may regulate cellular changes that cause either harm or benefit by producing cytokines or neurotrophins depending upon the primary cause and the circumstances during the inflammatory process of PD.
Hemmer B, Cepok S, Nessler S, Sommer N.
Pathogenesis of Multiple Sclerosis: An Update on Immunology.
Curr Opin Neurol 2002 15:227-31
Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R.
Psychoneuroimmunology: Psychological Influences on Immune Function and Health.
J Consult Clin Psychol 2002 70:537-47
Krueger JM, Obl, F. Jr., Fang J, Kubota T, Taishi P.
The Role of Cytokines in Physiological Sleep Regulation
Ann NY Acad Sci 2001 933: 211-221
Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS.
Role of Nitric Oxide in Inflammation-Mediated Neurodegeneration.
Ann N Y Acad Sci 2002 962:318-31
Mullington JM, Hinze-Selch D, Pollmcher T.
Mediators of Inflammation and Their Interaction with Sleep: Relevance for Chronic Fatigue Syndrome and Related Conditions
Ann NY Acad Sci 2001
Nakamura Y.
Regulating Factors for Microglial Activation.
Biol Pharm Bull 2002 25:945-53
Patarca R, Papper EM.
Cytokines and Chronic Fatigue Syndrome
Ann NY Acad Sci 2001 933: 185-200
Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmacher T
Cytokine-associated emotional and cognitive disturbances in humans.
Arch Gen Psychiatry 2001 58:445-52
Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, Dantzer R, Kelley KW.
Interleukin-10 in the Brain.
Crit Rev Immunol 2001 21:427-49
Virta M, Hurme M, Helminen M.
Increased Plasma Levels of Pro- and Anti-inflammatory Cytokines in Patients with Febrile Seizures
Epilepsia 2001 43:920-3
Yirmiya R, Pollak Y, Morag M, Reichenberg A, Barak O, Avitsur R, Shavit Y, Ovadia H, Weidenfeld J, Morag A, Newman ME, Pollmacher T.
Illness, Cytokines, and depression.
Ann N Y Acad Sci 2000 917:478-87
Yirmiya R.
Depression in medical illness: the role of the immune system.
West J Med. 2000 173:333-6.
Respiratory and Immune Modulation
Rennard SI. Antiinflammatory therapies other than corticosteroids. Proc Am Thorac Soc. 2004;1(3):282-7. University of Nebraska Medical Center, 985125 Nebraska Medical Center, Omaha, NE 68198, USA. srennard@unmc.edu
Antiinflammatory therapy for chronic obstructive pulmonary disease (COPD) can be directed at several stages of the inflammatory process. Much attention has been focused on blocking the damaging effects of toxic mediators released by inflammatory cells, including antioxidants and antiproteases. An alternate strategy is to block the recruitment of inflammatory cells into the lung, such as by inhibiting the production of chemotactic factors driving inflammatory cell recruitment, the ability of inflammatory cells to respond to chemotactic factors, and the ability of inflammatory cells to migrate. Moreover, mediators released by inflammatory cells, particularly tumor necrosis factor-alpha, probably have systemic effects in COPD. Blocking the release of these cytokines or blocking their ability to act on distal tissues represents another potential therapeutic option. It is also important to recognize that the various components of the inflammatory response are not independent. The action of proteases released by inflammatory cells, for example, can generate chemotactic factors, lead to activation of inflammatory cells, and modulate repair responses. The complex network of regulatory molecules that controls the inflammatory response, therefore, presents a number of potential therapeutic targets with the promise of altering the disease process in COPD.
Belvisi MG. Regulation of inflammatory cell function by corticosteroids. Proc Am Thorac Soc. 2004;1(3):207-14. Respiratory Pharmacology Group, Faculty of Medicine, Imperial College London, National Heart & Lung Institute, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK. m.belvisi@Imperial.ac.uk
Different inflammatory cell profiles are observed in the lungs of patients with asthma versus those with chronic obstructive pulmonary disease (COPD). In asthma, several key mediators have been implicated, including tumor necrosis factor-alpha and interleukin (IL)-1beta, together with cytokines derived from type 2 T-helper lymphocytes, such as IL-4, IL-5, and IL-13. In fact, inhibitors of IL-4 and IL-5 show promise as therapeutic agents. In COPD, the predominant inflammatory cell types are CD8(+) T lymphocytes, macrophages, and neutrophils. Glucocorticoids inhibit eosinophils in asthma, neutrophils in COPD and severe asthma, mast cells and basophils in asthma and COPD, and macrophages in COPD. However, it is generally assumed that neutrophils are less sensitive to glucocorticoids than are eosinophils and T cells, and that macrophages from patients with COPD are less sensitive to steroid treatment under certain circumstances. These differences in the responsiveness of activated inflammatory cells may help to explain why inhaled corticosteroid treatment has been more beneficial for patients with asthma than for patients with COPD.
Lazaar AL, Panettieri RA Jr. Airway smooth muscle: a modulator of airway remodeling in asthma. J Allergy Clin Immunol. 2005 Sep;116(3):488-95; quiz 496. Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine.
Asthma is a disease characterized, in part, by airway hyperresponsiveness and inflammation. Although asthma typically induces reversible airway obstruction, in some patients with asthma, airflow obstruction can become irreversible. Such obstruction might be a consequence of persistent structural changes in the airway wall caused by the frequent stimulation of airway smooth muscle (ASM) by contractile agonists, inflammatory mediators, and growth factors. Traditional concepts concerning airway inflammation have focused on trafficking leukocytes and on the effects of inflammatory mediators, cytokines, and chemokines secreted by these cells. Recent studies suggest that ASM cells might modulate airway remodeling by secreting cytokines, growth factors, or matrix proteins and by expressing cell adhesion molecules and other potential costimulatory molecules. These ASM cell functions might directly or indirectly modulate submucosal airway inflammation and promote airway remodeling.
Kampf, Caroline: Effects of Th-1 and Th-2 Cytokines and Reactive Oxygen Species on Normal Human Bronchial Epithelial Cells. - Uppsala Doctoral Dissertation 2001