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 driving the immune response towards T helper 1 (Th1) type responses which are characterized by high IFN-γ and low IL-4 production. In this study we investigated the effects of curcumin, a natural product of plants obtained from Curcuma longa (turmeric), on IL-12 production by mouse splenic macrophages and the subsequent ability of these cells to regulate cytokine production by CD4⁺ T cells. 2. Pretreatment with curcumin significantly inhibited IL-12 production by macrophages stimulated with either lipopolysaccharide (LPS) or head-killed Listeria monocytogenes (HKL). 3. Curcumin-pretreated macrophages reduced their ability to induce IFN-γ and increased the ability to induce IL-4 in Ag-primed CD4⁺ T cells. Addition of recombinant IL-12 to cultures of curcumin-pretreated macrophages and CD4⁺ T cells restored IFN-γ production in CD4⁺ T cells. 4. The in vivo administration of curcumin resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with either LPS or HKL, leading to the inhibition of Th1 cytokine profile (decreased IFN-γ and increased IL-4 production) in CD4⁺ 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 to a possible therapeutic use of curcumin in the Th1-mediated immune diseases.