Inhibition of Toxic Shock Syndrome Toxin-I-Induced Cytokine Production and

Toxic shock syndrome toxin-1 (TSST-1) induced production of the cytokines tumor necrosis factor-a (TNF-a), interleukin (IL)-1, IL-6, IL-2, and interferon-y (IFN-y) by human peripheral blood mononuclear cells (PBMC). In contrast, only low levels of IL-10 were present and IL-4 was absent in TSST-1-stimulated PBMC. Addition of1L-10 to TSST-1-stimulated PBMC inhibited the production of TNF-a, IL-1, IL-6, and IFN-y by 68%, 93%, 70%, and 86%, respectively, but had less effect (14%-37%) on T cell proliferation. IL-4 was less effective than IL-lO in inhibiting cytokine production and had no effect on T cell proliferation induced by TSST-1. Dexamethasone, an antiinflammatory agent, was the most potent agent in controlling TSST-1-mediated effects, as evidenced by inhibited T cell proliferation (>74%), reduced levels of cytokines (70%-84%), and reduced expression of CD25 and CD69 on PBMC. Thus, dexamethasone may be a useful agent to mitigate TSST-1-mediated toxic shock. Toxic shock syndrome toxin-I (TSST-I) is a pyrogenic exo-toxin produced by Staphylococcus aureus that causes toxic shock syndrome [I, 2]. The disease is characterized by fever, hypotension, desquamation of skin, and dysfunction of thre