INTERLEUKIN-1 RECEPTOR BLOCKADE REDUCES TUMOR-NECROSIS-FACTOR PRODUCTION, TISSUE-INJURY, AND MORTALITY AFTER HEPATIC ISCHEMIA-REPERFUSION IN THE RAT

The inflammatory cytokines interleukin (IL) 1 and tumor necrosis facto r (TNF) may play an important role in hepatic ischemia-reperfusion (I/ R) injury. To study the role of IL-1 in hepatic I-R injury, we investi gated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra ) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days, Rats were subjected to 90 min of par tial liver warm ischemia by clamping the vessels of the left and middl e lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before li ver ischemia was induced. IL-1 alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion, In a sec ond experiment to determine the effect of IL-1ra pretreatment on survi val rate, after 90 min of partial Liver ischemia, the right lateral an d caudate lobes were excised, leaving only the ischemic lobes, In both groups, IL-1 alpha was undetectable in blood, but increased in liver tissue, TNF increased in both blood and liver tissue as reperfusion ti me increased. Histological evidence of tissue injury was minimal in th e IL-1ra-treated group, Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared wi th the nontreated group, Survival rates in the IL-1ra-treated and nont reated group were 80% and 30%, respectively, The data demonstrated tha t the production of IL-1 and TNF increases in hepatic I-R injury and t hat pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.