LIPOSOME-ENTRAPPED PGE(1) POSTTREATMENT DECREASES IL-1-ALPHA-INDUCED NEUTROPHIL ACCUMULATION AND LUNG LEAK IN RATS

We found that treatment with liposome-entrapped prostaglandin E(1) (Lip-PGE(1)), but not with empty liposomes and/or free PGE(1), decreased the leak of intravascularly administered I-125-labeled albumin into lungs of rats given interleukin-1 alpha (IL-1 alpha) intratracheally. Lip-PGE(1) treatment also decreased lung myeloperoxidase activity, lung lavage neutrophil increases, and lung histological abnormalities found in rats given IL-1 alpha intratracheally. Interestingly, decreased lung leak and lung neutrophil accumulation occurred when Lip-PGE(1) was given intravenously 2.5 h after, but not immediately before, intratracheal IL-1 alpha administration. When Lip-PGE(1) treatment was given both before and 2.5 h after IL-1 alpha administration, lung leak was decreased to baseline levels. Lip-PGE(1) treatment given 2.5 h after IL-1 alpha administration also decreased lung oxidized glutathione levels, which increased in rats given IL-1 alpha intratracheally. We conclude that postinsult treatment with Lip-PGE(1) decreases lung leak, neutrophil recruitment, and oxidative responses in lungs of rats given IL-1 alpha intratracheally.