Inhibition of endogenous TNF formation by pentoxifylline.
During the last decade cytokines were recognized as focal components in acute and chronic inflammatory processes. The growing knowledge about these agents stimulated efforts to pharmacologically control their synthesis and action in clinical situations. Various rational approaches to these issues including selective antibodies or receptor antagonists are at present under clinical investigation. Recently, in our institute evidence was raised that pentoxifylline is able to suppress the synthesis of tumor necrosis factor-alpha in cell cultures, and in vivo, and to protect experimental animals against endotoxin shock. Extended studies in human experimental endotoxemia showed that pentoxifylline decreased circulating TNF without affecting endogenous formation of interleukins. The potency of this drug to interfere with TNF synthesis could also be demonstrated in cases of acute and chronic cytokine release-syndromes such as OKT3 first-dose reaction and severe pulmonary tuberculosis, respectively. In conclusion, we suggest that pentoxifylline may improve therapeutic strategies in septic syndrome and other diseases in which TNF represents a causative pathophysiological factor.
Zabel
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Department of Clinical Medicine, Forschungsinstitut Borstel, Germany.
Schade
F U
FU
Schlaak
M
M
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016030:Kidney Transplantation; D007970:Leukopenia; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010431:Pentoxifylline / Q000494:pharmacology*; D014115:Toxemia / Q000517:prevention & control; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014970:Xanthines / Q000494:pharmacology
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; D010431:Pentoxifylline; D007213:Indomethacin