Immunopathologic role of IL-17A and INF—γ in induced arthritis and therapeutic effect of Methotrexate-targeted nanoparticles on disease immunologic response.

Sahar Sobhy Abd Elhalem


Abstract


Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown etiology affecting about 1% of the world population. It is characterized by chronic inflammation of the synovial tissues of multiple joints leading to joint destruction and loss of function. Several induced animal models have been developed to aid the understanding of the disease process and for the development of therapeutic tools for intervention. One such model is pristane-induced arthritis (PIA) which is notable for its delayed onset of arthritis and resembles the joint inflammation and destruction seen in human RA. Obviously, rheumatoid arthritis was thought to be T-helper1 cell-associated disease. However, this view has dramatically changed after the discovery of T-helper 17 cells; these cells have emerged as an important mediator of human immune diseases such as rheumatoid arthritis. Th1-cells produce IFN γ and are important mediators of cell immune response to infectious agents and in some autoimmune disease models. INF-γ is the predominant cytokine in synovial tissues of RA patients. TH17 cells produce IL-17A which is a proinflammatory cytokine that has a direct effect on synovial fibroblasts and can induce production of proinflammatory mediators such as metalloproteinases, prostaglandins, chemokines, nitric oxide, and IL-6. Methotrexate (MTX), a folic acid antagonist, is one of the most important disease-modifying anti-rheumatic drugs and has become the predominant immunosuppressive agent used in the treatment of patients with RA. The use of MTX has been limited by some of its aggressive side effects such as hepatic cirrhosis, interstitial pneumonitis, myelosuppression, abdominal discomfort, alopecia and oral ulcerations.


Other data

Other Titles الدور المرضى المناعى للإنترليوكن-١٧ أ والإنترفيرون-جاما فى مرض آلام المفاصل و التأثير العلاجى للجزيئات النانونية المستهدفة الحاملة للميثوتريكسات على الإستجابة المناعية للمرض.
Issue Date 2014
URI http://research.asu.edu.eg/handle/12345678/47625


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