Liposome-entrapped PGE1 posttreatment decreases IL-1 alpha-induced neutrophil accumulation and lung leak in rats.
We found that treatment with liposome-entrapped prostaglandin E1 (Lip-PGE1), but not with empty liposomes and/or free PGE1, decreased the leak of intravascularly administered 125I-labeled albumin into lungs of rats given interleukin-1 alpha (IL-1 alpha) intratracheally. Lip-PGE1 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-PGE1 was given intravenously 2.5 h after, but not immediately before, intratracheal IL-1 alpha administration. When Lip-PGE1 treatment was given both before and 2.5 h after IL-1 alpha administration, lung leak was decreased to baseline levels. Lip-PGE1 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-PGE1 decreases lung leak, neutrophil recruitment, and oxidative responses in lungs of rats given IL-1 alpha intratracheally.
Leff
J A
JA
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
Baer
J W
JW
Kirkman
J M
JM
Bodman
M E
ME
Shanley
P F
PF
Cho
O J
OJ
Ostro
M J
MJ
Repine
J E
JE
D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004337:Drug Carriers; D005978:Glutathione / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007958:Leukocyte Count; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012711:Serum Albumin, Radio-Iodinated
D004337:Drug Carriers; D007375:Interleukin-1; D008081:Liposomes; D012711:Serum Albumin, Radio-Iodinated; D009195:Peroxidase; D000527:Alprostadil; D005978:Glutathione