CD4-CELL INDUCIBLE IMMUNOREGULATORY CYTOKINE RESPONSE IN RHEUMATOID-ARTHRITIS( T)

Objective, Monocytes and CD4+/CD8+ T cells produce immunoregulatory cy tokines that participate in the pathogenesis of various immune disorde rs. We investigated the secretion of Th1-Th2 cell response cytokine pr oduction of CD4+/CD8+ T cells from the synovial fluid (SF) and blood o f patients with rheumatoid arthritis (RA). Methods, Blood and SF purif ied monocytes, CD4+ and CD8+ T cells were stimulated with bacterial li popolysaccharides or anti-CD3 antibody, and secretion of various cytok ines was determined by bioassay or ELISA. Results. Monocytes from SF a nd blood of patients with RA produced highly elevated levels of interl eukin-l alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alp ha), and granulocyte macrophage colony stimulating factor (GMCSF), the leading mediators of inflammation. However, CD4+ T cells secreted def icient levels of IL-2 and interferon-gamma (IFN-gamma), but higher lev els of IL-4 and IL-10, the typical immunoregulatory Th2 cell response cytokines. CD8+ T cells also produce elevated levels of IL-4 and IL-10 but almost normal levels of IFN-gamma in this disease. Conclusion. Th e cytokine produced by monocytes (IL-alpha, IL-6, TNF-alpha, and GMCSF ) and by CD4+ T cells Th2 cell responses (IL-4 and IL-10) may exert im munopathologic and immunoregulatory effects in SF and thus mediate som e of the clinical manifestations of RA.