Pentoxifylline inhibits superantigen-induced toxic shock and cytokine release

Tumor necrosis factor alpha (TNF-alpha) is a critical cytokine that mediate s the toxic effects of bacterial superantigens like staphylococcal enteroto xin B (SEB) and toxic shock syndrome toxin 1 (TSST-1), Pentoxifylline, an a nti-inflammatory agent that inhibits endotoxemia and lipopolysaccharide (LP S)-induced release of TNF-alpha, was tested for its ability to inhibit SEB- and TSST-1-induced activation of human peripheral blood mononuclear cells (PBMCs) in vitro and toxin-mediated shock in mice. Stimulation of PBMCs by SEE or TSST-1 was effectively blocked by pentoxifylline (10 mM), as evidenc ed by the inhibition of TNF-alpha, interleukin 1 beta (IL-1 beta), gamma in terferon (IFN-gamma), and T-cell proliferation. The levels of TNF-alpha, IL -1 alpha, and IFN-gamma in serum after an SEE or TSST-1 injection were sign ificantly lower in mice given pentoxifylline (5.5 mg/animal) versus control mice. Additionally, pentoxifylline diminished the lethal effects and tempe rature fluctuations elicited by SEE and TSST-1, Thus, in addition to treati ng endotoxemias, the cumulative in vitro and in vivo data suggest that pent oxifylline may also be useful in abrogating the ill effects of staphylococc al enterotoxins and TSST-1.