engleski

Protective effect of IL-1 alpha and beta on the acetaminophen induced liver toxicity relies on their early induction by acetaminophen itself.

We have previoulsy shown that both IL-1 alpha and IL-6 exhibit heaptopreotective effect if given before administration of acetaminophen (APAP) that is partially mediated by PGE2. When the effect of IL-1 beta was investigated using the same model, IL (1500IU/mouse)or anti-IL-1beta antibody (0.5ml of rabbit to mouse IL-1, obtained by three constitutive injection of Il-1 beta, first incomplete FCA) were given i.p. 3 hours before APAP. The survival of mice has been followed for 72 hours and the serum concetration of aminotransfereses (AST and ALT) were determined 18-24 hours after APAP administration. IL-1beta significantl< increased the survival of mice and decreased serum level of AST and ALT (p<0.05. As expected, when anti IL-1Ra antibody was administered, significant increase in the serum concentrations of AST and ALT (p<0.05 or better) were observed. The survival of animals hasn't been followed in this experiment. The finding that anti-IL-1R alpha antiobdy treatment causes increased AST and ALT serumlevel, the same effect as anti-IL-1 beta therapy dose, prompted us to analyze the endogenous synthesis of Il-1 cytokine in liver samples from IL-1 non-exposed but APAP intocicated animals. RT_PCR analysis of the IL-1a alpha nd IL-1 beta expression level in liver smaples from APAP inotxicated mice has revealed that acetaminophen induces the expression of both cytokines though of somewhat different pattern, already 1 hour after its intragastric administration. This expression was even higher at 6 hours following APAP adminsitration and could be blocked by intraperitoneal injection of aspirin at the dose which inhibits NF-kB activity. Based on this we hypothesized that oganism intoxicated with APAP synthesize its own IL-1 realy on following APAP administration which may represent a host defense raction that could be halped by applying appropriate dose of exogenous cytokines.

acetaminphen; IL-1 hepatoprotective effect; RT-PCR analysis

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