New Approaches in Immunotherapy of Beh?et Disease

摘要

Beh.et Disease (BD) is an autoimmune disorder with recurrent ocular, vascular, central nervous system, articular, mucocutaneous, and gastrointestinal manifestations with unclear etiology and pathogenesis. The further characterization of inflammatory features of Beh.et's disease may eventually lead to development of better treatment options. Clinical and laboratory observations suggested an important role of IL-17, IL-21 and neutrophil-mediated process in the pathogenesis of BD.New therapeutic modalities target specific and nonspecific suppression of the immune system. The various non-specific immunosuppressive drugs, used either alone or in combinations, frequently fail to control inflammation or maintain remissions. Due to encouraging clinical results (i.e. Antigenic specification, prolonged survival with acceptable levels of toxicity); antibody-based drugs co uld be effective for the clinical management of Beh.et's disease. var currentpos,timer; function initialize() { timer=setInterval("scrollwindow()",10);} function sc(){clearInterval(timer); }function scrollwindow() { currentpos=document.body.scrollTop; window.scroll(0,++currentpos); if (currentpos != document.body.scrollTop) sc();} document.onmousedown=scdocument.ondblclick=initialize10 |Zare Shahnehet al.Advanced Pharmaceutical Bulletin,2013, 3(1),9-11Copyright . 2013by Tabriz University of Medical Scienceselimination. Functional abnormalities in any steps of these may cause following defective response in immune system.10Hyperactivity of the neutrophils is an important aspect of the immunological abnormalities in BD.Before going directly to neutrophils function in lesions of BD, proof of concept studies relevant if perspectives are needed.Biopsy specimens from active lesions of BD display large amounts of neutrophils in the absence of infection, and neutrophils from patients with BD show increased superoxide anion production, enhanced chemotaxis, and excessive release of granular enzymes, which indicate neutrophil hyperactivity in BD.11 Several proinflammatory cytokines, such as interleukin 17 and 21 are proposed to be accounted for the priming of neutrophil activation and the enhanced cellular interactions between neutrophils and endothelial cells. Moreover, IL-17 involved in the recruitment of neutrophils to the site of inflammation.12,13Neutrophil hyperactivity and elevated inflammatory cytokine levels are hallmarks of BD. Neutrophils produce inflammatory cytokines, which promote neutrophil activity. This makes a cycle in which elevated and activated neutrophils produce more cytokines and the latter enhance neutrophil activity.14The primary goals of BD management are symptom control, soothing the inflammation and suppression of the immune system and prevention of end-organ damage. The treatment options must be anti-inflammatory agents and immunosuppressant but in severe stages, may be resistant to all forms of immunosuppression. Conventional therapeutic approaches suppress the activity of the leucocytes and lymphocytes.15Drugs are frequently used in combination to maximize efficacy while minimizing side effects. Conventional therapeutic approaches suppress the activity of the leucocytes (anti-inflammatory) and lymphocytes (immunosuppressive) in T-cell-mediated diseases. Now colchicine has been widely used as a basic drug for treatment of Beh.et's disease and applies beneficial effects through inhibition of neutrophil functions as well as neutrophils chemotaxis.16In this era, by the advent of Monoclonal antibodies (mAb) directed against any antigens of interest, Immunodrugs (drug immunoconjugates), Immunocytokines (Recombinant mAb-cytokine fusion proteins), immunotherapy based on mAb-therapy of human autoimmune disease have been introduced.17During the last ten-year period, Infliximab (chimeric anti-TNF-|ámonoclonal antibody), Adalimumab (humanized anti-TNF-|ámonoclonal antibody) and Etanercept (fusion protein human p75 TNF-|á receptor IgG1) are increasingly used for patients with BD. Because clinical and laboratory observations suggested that TNF-mediated process in the pathogenesis of BD.18The further characterization of inflammatory features of Beh.et's disease may eventually lead to development of better treatment modalities. Clinical and laboratory observations proposed a central role of IL-17 and IL-21 and neutrophil-mediated process in the pathogenesis of BD. This result indicates correlation between neutrophil biology, IL-17 and, IL-21 with Beh.et's disease. Considering the fact that if in new studies, researcher focuses in these perspectives, it could be possible find better aspect in Beh.et's disease therapy based on its immunophatogenesis. Due to encouraging clinical results (i.e. Antigenic specification, prolonged survival with acceptable levels of toxicity); antibody-based drugs could be effective for the clinical management of Beh.et's disease. References 1.Davatchi F. Diagnosis/Classification Criteria for Behcet's Disease. Patholog