Production of Tumor Necrosis Factor by Human Monocytes in Response to Toxic-Shock-Syndrome Toxin-1

We studied the effect of toxic-shock-syndrome toxin-1 (TSST-1) on production of tumor necrosis factor (TNF) by human monocytes. Adherent mononuclear cells were stimulated with TSST-1 and their supernatants assayed for TNF by using L929 cells in a cytotoxicity assay. TSST-1 stimulated production of TNF over a wide range of concentrations. The cytotoxicity of monocyte supernatants was neutralized by antibody to TNF but not by antibody to interleukin-1 or by normal rabbit serum. TSST-1 and lipopolysaccharide (LPS) had a synergistic effect on monokine production. Monocytes "primed" with TSST-1 produced more interleukin-1 and TNF in response to LPS than did unprimed cells. Treating monocytes with LPS before TSST-1 and co-incubating the two agents with cells for 24 h also enhanced monokine production under some circumstances. These studies suggest a role for TNF in the pathogenesis of toxic shock syndrome, as a consequence of induction by TSST-1 alone or the synergistic effects of several bacterial products.