The immune response identified by the induction of Th1/Th2 cells plays a critical role in the pathogenesis of various inflammatory and immune disorders. We have determined that in children with systemic onset juvenile rheumatoid arthritis (JRA), peripheral blood mononuclear cells (PBMC) constitutively and after stimulation with various antigens in vitro induce a higher secretion of interleukin-4 (IL-4) and IL-10 with a characteristic deficiency of IL-2 and interferon-gamma (IFN-gamma). This cytokine pattern is a representative of a mixed Th1/Th2 cell response in JRA. The CD3/CD28 costimulatory molecule was found to be a potent inducer of IL-4 and IL-10 secretion. PBMC-derived augmented IL-10 secretion was inhibited by exogenous Th1 cell type recombinant cytokines (IL-2, IL-12, and IFN-gamma). Although IL-10 inhibits PBMC-induced proinflammatory IL-1alpha and tumor necrosis factor-alpha secretion, it had no major effect on IL-6 production. The finding of a distinctly enhanced mixed Th1/Th2 cell response cytokine (IL-4 and IL-10) pattern in JRA provides a framework for developing strategies for immunologic intervention in this rheumatic disorder in children.
Copyright 1998 Academic Press.