Endotoxin Enhancement of Toxic Shock Syndrome Toxin I-Induced Secretion of Interleukin 1 by Murine Macrophages

The purpose of this study was to determine whether endotoxin could augment toxic shock syndrome toxin 1 (TSST-l)-induced production of interleukin 1 (IL-1) by murine macrophages. Macrophages from C3H/HeJ or C57B1/6 mice were stimulated with purified TSST-1 alone or in combination with lipopolysaccharide (LPS). A dramatic synergistic thymocyteproliferative response was induced by supernatants from C57B1/6 macrophages stimulated with both TSST-1 and LPS. No enhanced response was induced by supernatants from C3H/HeJ macrophages. A portion of the enhanced response induced by C57B1/6 macrophage supernatants was attributed to synergism between IL-1 and residual TSST-1 in the thymocyte assay. The addition of monoclonal antibody to TSST-1 to the supernatants eliminated the effects of residual TSST-1 in the thymocyte assay and demonstrated a synergistic induction of IL-1. These data (1) show that LPS can enhance macrophage responsiveness to TSST-1; (2) suggest that TSST-1 not only induces IL-1 secretion but also enhances target cell responsiveness to IL-1; and (3) further support the role of IL-1 in the pathogenesis of toxic shock syndrome.