Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza

Pharmacological control of interleukin-12 (IL-12) and interferon-gamma (IFN -gamma) production may be a key therapeutic strategy for modulating immunol ogical diseases dominated by Th1-derived cytokine responses. In this study, we investigated the effects of three different tanshinone pigments from Sa lvia miltiorrhiza (tanshinone I, dihydrotanshinone, and cryptotanshinone) o n IL-12 production in mouse macrophages and on IFN-gamma production in lymp h node cells. All tested tanshinones significantly inhibited IL-12 producti on in lipopolysaccharide (LPS)-activated macrophages and also IFN-gamma pro duction in keyhole limpet hemocyanin (KLH)-primed lymph node cells in a dos e-dependent manner. Dihydrotanshinone was more effective than tanshinone I or cryptotanshinone. Tanshinones significantly inhibited the expression of IL-12 p40 gene at the mRNA level. Furthermore, tanshinones potently inhibit ed the promoter activation of IL-12 p40 gene and nuclear factor (NF)-kappa B binding to the kappa B Site, suggesting that tanshinones may negatively r egulate IL-12 production at the transcription level. These results may expl ain some known biological activities of tanshinones including their anti-in flammatory effect, and suggest a possible use of tanshinones in the treatme nt of immunological diseases dominated by Th1-derived cytokine responses. ( C) 2000 Elsevier Science B.V. All rights reserved.