Corticotropin-releasing factor reduces lipopolysaccharide-induced pulmonary vascular leak.
Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p = .08). These data indicate the potential utility of CRF as a modulator of pulmonary vascular leak.
Kelley
D M
DM
Division of Pulmonary and Critical Care Medicine, West Los Angeles Veterans Administration Medical Center, California 90073.
Lichtenstein
A
A
Wang
J
J
Taylor
A N
AN
Dubinett
S M
SM
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control*
D008070:Lipopolysaccharides; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone