Toxic Shock Syndrome is Mediated by Interleukin 1 and Tumor Necrosis Factor

Abstract

Toxic shock syndrome toxin 1 (TSST-1) induction of interleukin 1 (IL-1) secretion in the human and the rabbit has previously been demonstrated. Stimulation of the secretion of tumor necrosis factor (TNF) by TSST-1 in the human and the rabbit in vitro and in vivo is now reported. TNF (2-jg/kg bolus) and IL-1 (2to 5-jig/kg bolus) induce a sharp fall of mean arterial pressure (MAP) in the rabbit within 10-15 minutes. Associated with the fall in MAP, decreases in the systemic vascular resistance (SVR) and central venous pressure (CVP) were observed, while cardiac output and heart rate increased. Intravenous injection of 2 jg of TSST-1/kg into the rabbit induced significant decreases in MAP and SVR and an increase in CVP. The dose of 5 jg/kg caused a shock-like state followed by death. High serum TNF levels in the TSST-l-injected rabbits were detected by use of a cytotoxicity test with L929 cells. The bioassay also demonstrated the secretion of TNF from culture supernatants of rabbit mononuclear cells (MNCs) that were stimulated with TSST-1. Both the radioimmunoassay and the bioassay showed a significant TNF secretion from human MNCs; 1 ng of TSST-1/mL induced 800 pg of TNF/mL. Combined administration of IL-1 and TNF (each with a 1-jg/kg bolus and a 5 ng/[kg-min] infusion for 2 hours) in the rabbit caused a shock-like state with a more profound and sustained fall into MAP than did single administration of IL-1 or TNF These results demonstrate that TSST-1 induces the secretion of IL-1 and TNF by human and rabbit MNCs and that IL-1 and TNF act synergistically to induce a profound shock-like state.