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 chronic inflammatory autoimmune disorders. In this study we investigated the effects of sulfasalazine, a drug for treating inflammatory bowel disease and rheumatoid arthritis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Sulfasalazine potently inhibited the production of IL-12 in a dose-dependent manner, in part through the down-regulation of nuclear factor kappaB (NFkappaB) activation in IL-12 p40 gene. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the kappaB site, which significantly decreased upon addition of sulfasalazine as demonstrated by an electrophoretic gel shift assay. Importantly, macrophages pretreated with sulfasalazine either in vitro or in vivo reduced their ability to induce interferon-gamma (IFN-gamma) and increased 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 cells by suppressing IL-12 production in macrophages, and sulfasalazine-induced inhibition of IL-12 production in macrophages may explain some of the known biological effects of sulfasalazine.
Kang
B Y
BY
College of Pharmacy, Chonnam National University, Kwangju, Republic of Korea.
Chung
S W
SW
Im
S Y
SY
Choe
Y K
YK
Kim
T S
TS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D012460:Sulfasalazine / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D018664:Interleukin-12; D012460:Sulfasalazine