Coordinate suppression of superantigen-induced cytokine production and T-cell proliferation by a small nonpeptidic inhibitor of class II major histocompatibility complex and CD4 interaction.
Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). TJU103, a small nonpeptidic molecule that blocks the interaction between major histocompatibility complex class II and CD4 molecules inhibited SE-stimulated T-cell proliferation (by 92%) and production of tumor necrosis factor, interleukin 1beta, interleukin 6, and gamma interferon (by 66, 56, 76, and 72%, respectively) by human peripheral blood mononuclear cells. These data suggest that TJU103 may be useful for mitigating the pathogenic effects of SE.
Krakauer
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Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. teresa.krakauer@det.amedd.army.mil
D015704:CD4 Antigens / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005098:Exotoxins / Q000494:pharmacology; D005802:Genes, MHC Class II / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects; D009930:Organic Chemicals / Q000494:pharmacology*; D013210:Staphylococcus / Q000378:metabolism; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015704:CD4 Antigens; D016207:Cytokines; D005098:Exotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D009930:Organic Chemicals; D018089:Superantigens; C407006:TJU 103; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma