Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1β, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1α, and MIP-1β by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins. Copyright © 2005 Taylor &, Francis Inc.