Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon.

Abstract

We present evidence that toxic shock syndrome toxin 1 (TSST-1) induces the production of high levels of TNF by human blood monocytes. Enriched lymphocyte preparations incubated with the staphylococcal toxin produced significant levels of TNF-like activity that is not neutralized by anti-rHuTNF antibodies and is likely to be lymphotoxin (LT or TNF-beta). We demonstrate also that TSST-1 is a potent inducer of IFN-gamma. When lymphocyte preparations were costimulated with PMA, the TSST-1 effect was strongly potentiated and the levels of cytotoxic factors, IFN-gamma, and IL-2 present in supernatant fluids were comparable to those observed after treatment with PMA and PHA. Thus, TSST-1, which is also known as an inducer of IL-1 and IL-2, stimulates the production of endogenous mediators that could play a role in the physiopathological processes of toxic shock syndrome (TSS). The described results suggest that the discrepancies in the clinical features between TSS and endotoxin shock may be related to qualitative differences in cytokine production.

Induction by Toxic-Shock-Syndrome Toxin-1 of a Circulating Tumor Necrosis Factor-Like Substance in Rabbits and of Immunoreactive Tumor Necrosis Factor and Interleukin-1 from Human Mononuclear Cells

“…Recently two groups reported the production of TNF by human blood MNCs [28,29] by using the L929 cytotoxicity assay. Our results extend these studies by showing that TSST-1 induces TNF, IL-1 a, and IL-1 (3 from MNCs, as determined by specific RIAs.…”

Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline

“…Their interactions with cells of the immune system initiate a massive production of the proinflammatory cytokines, tumor-necrosis factor ␣ (TNF-␣), interferon-␥ (IFN-␥), and interleukin-1 (IL-1). Both the hyperactivation of T cells and the excessive production of proinflammatory cytokines are responsible for the pathogenesis of toxic shock and various autoimmune disorders [2][3][4][7][8][9].…”

Involvement of HLA class II molecules in acquisition of staphylococcal enterotoxin A-binding activity and accessory cell activity in activation of human T cells by related toxins in vascular endothelial cells

“…It was reported that HLA class IP cells eould be killed by T cells reactive to SEs through the interaction among TCR, exotoxins and class II moleeules [II]. Tumour necrosis faetor-bcta induced by TSST-1 [29] could also be harmful to VEC. The consecutive chains of these biological reactions would result in the development of vaseulitis.…”