Curcumin inhibits Th1 cytokine profile in CD4(+) T cells by suppressing interleukin-12 production in macrophages

1 Interleukin-12 (IL-12) plays a central role in the immune system by drivi ng the immune response towards T helper 1 (Th1) type responses which are ch aracterized by high IFN-gamma and low IL-4 production. In this study we inv estigated the effects of curcumin, a natural product of plants obtained fro m Curcuma longa (turmeric), on IL-12 production by mouse splenic macrophage s and the subsequent ability of these cells to regulate cytokine production by CD4(i) T cells. 2 Pretreatment with curcumin significantly inhibited IL-12 production by ma crophages stimulated with either lipopolysaccharide (LPS) or head-killed Li steria monocytogenes (HKL). 3 Curcumin-pretreated macrophages reduced their ability to induce IFN-gamma and increased the ability to induce IL-4 in Ag-primed CD4(+) T cells. Addi tion of recombinant IL-12 to cultures of curcumin-pretreated macrophages an d CD4+ T cells restored IFN-gamma production in CD4(+) T cells. 4 The in vivo administration of curcumin resulted in the inhibition of IL-1 2. production by macrophages stimulated in vitro with either LPS or HKL, le ading to the inhibition of Th1 cytokine profile (decreased IFN-gamma and in creased IL-4 production) in CD4(i) T cells. 5 These findings suggest that curcumin may inhibit Th1 cytokine profile in CD4(+) T cells by suppressing IL-12 production in macrophages, and points t o a possible therapeutic use of curcumin in the Th1-mediated immune disease s.