By. Kang et al., Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages, IMMUNOLOGY, 98(1), 1999, pp. 98-103
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.