CORTICOTROPIN-RELEASING FACTOR REDUCES LIPOPOLYSACCHARIDE-INDUCED PULMONARY VASCULAR LEAK

Previous studies have suggested that corticotropin-releasing factor (C RF) has immunoregulatory effects in addition to its neuroendocrine rol e. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)- induced pulmonary vascular leak in vivo. Female BALB/C mice were treat ed with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measuremen t of lung wet-to-dry ratios. The stress-induced increase in serum cort icosterone levels in mice injected with LPS alone was not further incr eased 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 infiltrati on was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survi val was demonstrated in CRF-treated mice following challenge with LPS (p=.08). These data indicate the potential utility of CRF as a modulat or of pulmonary vascular leak.