Induction of human interleukin-1 by toxic-shock-syndrome toxin-1

Strains of Staphylococcus aureus isolated from patients with toxic shock syndrome (TSS) make a characteristic protein known as toxic-shock-syndrome toxin-1 (TSST-1), but the role of this protein in the pathogenesis of TSS is not certain. We have purified TSST-1 by using a combination of alcohol precipitation, isoelectric focusing, and gel chromatography. TSST-1 has an isoelectric point of 7.2 and a molecular weight of 23,100, in accordance with previously published determinations for this protein, and is serologically identical to pyrogenic exotoxin C and staphylococcal enterotoxin F. In highly purified form, TSST-1 is a potent inducer of interleukin-1 production by human monocytes, as quantitated in a thymocyte-proliferation assay. This capability is not attributable to contamination by other staphylococcal products or gram-negative endotoxin and can be blocked by hydrocortisone. Many features of TSS suggest that induction of interleukin-1 by TSST-1 in vivo may play a central role in the elaboration of this disease.