Interleukin-1 pretreatment prevents interleukin-1-induced lung leak in rats.
We found that rats pretreated with interleukin-1 (IL-1) intraperitoneally did not develop the acute oxidative, neutrophil-dependent lung leak that occurs after administration of IL-1 intratracheally (IL-1-induced tolerance). IL-1-pretreated rats also had increased lung catalase and glucose-6-phosphate dehydrogenase (G6PDH) activity and increased plasma catalase activity compared with sham-pretreated rats. In contrast to reducing lung leak, IL-1 pretreatment did not reduce the numbers of neutrophils that are increased in lung lavages of rats given IL-1 intratracheally. IL-1-induced tolerance to IL-1-mediated lung leak and the associated increases in lung catalase, lung G6PDH, and serum catalase activities were all prevented by treating rats with the IL-1-receptor antagonist or with N-acetyl-L-cysteine, an agent that increases intracellular glutathione levels. Our results indicate that IL-1 pretreatment confers tolerance to IL-1-mediated lung leak without decreasing IL-1-induced increases in lung neutrophils. The possible protective actions of IL-1 should be considered in experiments and clinical trials where IL-1 activity is reduced pharmacologically.
Webb-Waring Institute for Biomedical Research, Denver, Colorado 80262.
J A
JA
Leff
C P
CP
Wilke
M J
MJ
Furman
M E
ME
Bodman
J E
JE
Repine
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002374:Catalase / Q000097:blood / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D007507:Therapeutic Irrigation
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D002374:Catalase; D000111:Acetylcysteine