Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages

Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper 1 (Th1) immune response, which may be involved in the pathogenesis of chron ic inflammatory autoimmune disorders. In this study we investigated the eff ects of sulfasalazine, a drug for treating inflammatory bowel disease and r heumatoid arthritis, on the production of IL-12 from mouse macrophages stim ulated with lipopolysaccharide (LPS). Sulfasalazine potently inhibited the production of IL-12 in a dose-dependent manner, in part through the down-re gulation of nuclear factor kappa B (NF kappa B) activation in IL-12 p40 gen e. Activation of macrophages by LPS resulted in markedly enhanced binding a ctivities to the kappa B site, which significantly decreased upon addition of sulfasalazine as demonstrated by an electrophoretic gel shift assay. Imp ortantly, macrophages pretreated with sulfasalazine either in vitro or in v ivo reduced their ability to induce interferon-gamma (IFN-gamma) and increa sed the ability to induce IL-4 in antigen-primed CD4(+) T cells. From these results, sulfasalazine may induce the Th2 cytokine profile in CD4(+) T cel ls by suppressing IL-12 production in macrophages, and sulfasalazine-induce d inhibition of IL-12 production in macrophages may explain some of the kno wn biological effects of sulfasalazine.