Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptide with vasodilator, bronchodilator, and anti-inflammatory effects. Little is known about pro-inflammatory effects of VIP. We investigated the 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 h, caused dose-related increases of IL-6 (98% increase above control, P < 0.001) and IL-8 (35% increase above control, P < 0.01). After 4 h of incubation, 10(-7) M PHI also increased IL-6 release by 74% (P < 0.01). After 8 h of incubation, VIP increased IL-6 release by 59% (P < 0.01), causing no effect on IL-8 release. After 24 h of incubation, VIP increased 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 that increases in response to VIP stimulation occurred by 1 h and persisted through 16 h of stimulation. VIP had no significant effect on the release of G-CSF and GM-CSF. VIP did not induce cell proliferation at 24 and 48 h. These findings suggest that VIP can alter epithelial cell cytokine release and might be capable of modulating the airway inflammatory response in this manner.