engleski

Protection of acute hepatotoxicity in mice by interleukin-1α - the role of interleukin-6 and prostaglandin E2

Background and Purpose. We have shown previously that IL-la is highly protective in mice with acute hepatototoxicity induced by AAP In these experiments we investigated whether PCE2 and IL-6 are involved in IL-la-induced hepatoprotection. In addition, we investigated the effect of spontaneously produced IL-6 on AAP-induced hepatotoxicity, and the ef&not ; fect of IL-la on heptotoxicity induced by LPS in D-galactosamine sensi&not ; tized mice. Materials and Methods. The mice received toxic dose of AAP by gas&not ; tric route. Recombinant human IL-lα or recombinant mouse IL-6 were given to mice i.p. 2 hours before AAP polycolnal anti-PGE2 and mono&not ; clonal anti-IL-6 antibodies were given 3 hours before IL-lα , or, when given alone, 5 hours before AAP The mortality of mice was followed, and serum aminotransferase levels (AST and ALT) were determined 24 hours after the AAP administration. Results. IL-lα significantly reduced and the serum ALT and AST levels in the AAP-treated mice. It also decreased the mortality of mice which re&not ; ceived LPS after D-galactosamine. Pretreatment of mice with anti-PGE2 or anti-IL-6 antibodies before IL-lα administration decreased its protective effect in those with AAP-induced hepatotoxicity. Administration of anti-IL-6 antibodies alone before AAP increased the mortality of mice and the se&not ; rum aminotransferase levels, while, in contrast, administration of recombinant mouse IL-6 before AAP had the opposite, i.e. beneficial effect. Conclusion. Both PGE2 and IL-6 mediate, perhaps in mutually interde&not ; pendent way, the hepatoprotective effect of IL-lα .

acetaminophen; hepatotoxicity; interleukin-lα; interleukin-6; prostaglandin E2; D-galactosamine; lipopolysaccharide

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