VASOACTIVE-INTESTINAL-PEPTIDE (VIP) INDUCES IL-6 AND IL-8, BUT NOT G-CSF AND GM-CSF RELEASE FROM A HUMAN BRONCHIAL EPITHELIAL-CELL LINE

Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptid e with vasodilator, bronchodilator, and anti-inflammatory effects. Lit tle is known about pro-inflammatory effects of VIP. We investigated th e effect of VIP on the secretion of IL-6, IL-8, GM-CSF, and G-CSF from a bronchial epithelial cell line (BEAS 2B). The incubation of BEAS-2B cells with VIP in concentrations of 10(-13) to 10(-7) M for 4 hr caus ed dose-related increases of IL-6 (98% increase above control, P < 0.0 01) and IL-8 (35% increase above control, P < 0.01). After 4 h of incu bation, 10(-7) M PHI also increased IL-6 release by 74% (P < 0.01). Af ter 8 h of incubation, VIP increased IL-6 release by 59% (P < 0.01), c ausing no effect on IL-8 release. After 24 h of incubation, VIP increa sed the release of IL-6 by 48% (P < 0.05) and IL-8 by 45% (P < 0.05). Ribonuclease protection assays for steady-state IL-6 mRNA revealed tha t increases in response to VIP stimulation occurred by 1 h and persist ed through 16 h of stimulation. VIP had no significant effect on the r elease of G-CSF and GM-CSF. VIP did not induce cell proliferation at 2 4 and 48 h. These findings suggest that VIP can alter epithelial cell cytokine release and might be capable of modulating the airway inflamm atory response in this manner.