THE EFFECT OF VASOACTIVE-INTESTINAL-PEPTIDE ON PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA (IN-VIVO)

is known that vasoactive intestinal peptide (VIP) increases the level of adenosine 3'5'cyclic monophosphate (cAMP) in mononuclear cells and that most agents that increase cAMP in these cells inhibit the product ion of tumor necrosis factor(TNF)-alpha. Therefore, we investigated th e production of TNF-alpha in mice that were pretreated with VIP. The e ffect of VIP on TNF-alpha production was determined in three different experimental models: in normal mice given lipopolysaccharide (LPS), i n Calmette-Guerin bacteria-pretreated mice given LPS and in mice infec ted with Escherichia coli. In all models, TNF-a was determined in pool ed sera obtained from four to six mice per group, by bioassay with sen sitive L929 cells. In all three models, the TNF-alpha level was four t o 15 times lower in mice pretreated with VIP than in control mice pret reated with phosphate-buffered saline. In further experiments, we will investigate the dose- and time-response to VIP, as well as the effect of VIP on the survival of mice treated as in the second and third mod els.