INTERLEUKIN-1 PRETREATMENT PREVENTS INTERLEUKIN-1-INDUCED LUNG LEAK IN RATS

We found that rats pretreated with interleukin-1 (IL-1) intraperitonea lly did not develop the acute oxidative, neutrophil-dependent lung lea k that occurs after administration of IL-1 intratracheally (IL-1-induc ed tolerance). IL-1-pretreated rats also had increased lung catalase a nd glucose-6-phosphate dehydrogenase (G6PDH) activity and increased pl asma catalase activity compared with sham-pretreated rats. In contrast to reducing lung leak, IL-1 pretreatment did not reduce the numbers o f neutrophils that are increased in lung lavages of rats given IL-1 in tratracheally. IL-1-induced tolerance to IL-1-mediated lung leak and t he associated increases in lung catalase, lung G6PDH, and serum catala se activities were all prevented by treating rats with the IL-1-recept or antagonist or with N-acetyl-L-cysteine, an agent that increases int racellular glutathione levels. Our results indicate that IL-1 pretreat ment confers tolerance to IL-1-mediated lung leak without decreasing I L-1-induced increases in lung neutrophils. The possible protective act ions of IL-1 should be considered in experiments and clinical trials w here IL-1 activity is reduced pharmacologically.