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Clinical and Diagnostic Laboratory Immunology, July 1999, p. 594-598, Vol. 6, No. 4
1071-412X/99/$04.00+0

Pentoxifylline Inhibits Superantigen-Induced Toxic Shock and Cytokine Release

Teresa Krakauer* and Bradley G. Stiles

Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011

Received 23 November 1998/Returned for modification 9 March 1999/Accepted 23 April 1999

Tumor necrosis factor alpha (TNF-alpha ) is a critical cytokine that mediates the toxic effects of bacterial superantigens like staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSST-1). Pentoxifylline, an anti-inflammatory agent that inhibits endotoxemia and lipopolysaccharide (LPS)-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 SEB or TSST-1 was effectively blocked by pentoxifylline (10 mM), as evidenced by the inhibition of TNF-alpha , interleukin 1beta (IL-1beta ), gamma interferon (IFN-gamma ), and T-cell proliferation. The levels of TNF-alpha , IL-1alpha , and IFN-gamma in serum after an SEB or TSST-1 injection were significantly lower in mice given pentoxifylline (5.5 mg/animal) versus control mice. Additionally, pentoxifylline diminished the lethal effects and temperature fluctuations elicited by SEB and TSST-1. Thus, in addition to treating endotoxemias, the cumulative in vitro and in vivo data suggest that pentoxifylline may also be useful in abrogating the ill effects of staphylococcal enterotoxins and TSST-1.

* Corresponding author. Mailing address: Department of Immunology and Molecular Biology, Bldg. 1425, USAMRIID, Fort Detrick, Frederick MD 21702-5011. Phone: (301) 619-4733. Fax: (301) 619-2348. E-mail: terry_krakauer{at}detrick.army.mil.

Clinical and Diagnostic Laboratory Immunology, July 1999, p. 594-598, Vol. 6, No. 4
1071-412X/99/$04.00+0


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  • Nakagawa, S., Kushiya, K., Taneike, I., Imanishi, K., Uchiyama, T., Yamamoto, T. (2005). Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin 1 (TSST-1), Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice. CVI 12: 399-408 [Abstract] [Full Text]  
  • Hale, M. L., Margolin, S. B., Krakauer, T., Roy, C. J., Stiles, B. G. (2002). Pirfenidone Blocks the In Vitro and In Vivo Effects of Staphylococcal Enterotoxin B. Infect. Immun. 70: 2989-2994 [Abstract] [Full Text]  


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