Effect of substance P on immunoglobulin and interferon-gamma secretion by cultured human duodenal mucosa.

ABSTRACT

Recently, we have demonstrated a substance P (SP)-dependent modulation of in vitro IgM and interferon-gamma (IFN-gamma) secretion by human peripheral blood mononuclear cells, as well as lymphokine activities in supernatants of cultured duodenal mucosa. Therefore we investigated other local immunoregulatory effects of SP. Duodenal biopsies of 7 healthy subjects were cultured with Pokeweed mitogen (PWM, 1 microgram/ml) for 4 days at 37 degrees C in 1 ml medium each. SP was added in concentrations ranging from 10(-12)M to 10(-6)M on day 1. Fresh media with fresh PWM were added every day. IgG, IgM, IgA (ELISA) and IFN-gamma (RIA) were determined in the culture supernatants. Values were referred to 5 mg biopsy weight and expressed as % change in basal PWM pulsed secretion, or as units/ml. 10(-6) M and 10(-12) M SP increased secretion of all immunoglobulin isotypes. Compared to controls, 10(-6) M and 10(-12) M SP led to an increase in IgM secretion of up to 73 +/- 23% and 41 +/- 32% and to an increase in IgA secretion up to 96 +/- 35% and 25 +/- 33%, respectively (alpha = 0.02 for both isotypes at 10(-6) M). 10(-12) M to 10(-6) M SP led to a significant dose-dependent increase in IFN-gamma secretion from 7.08 +/- 1.65 up to 21.8 +/- 12.6 units/ml/5 mg. The maximum effect could be seen on culture days 3 and 4. We were able to demonstrate for the first time that SP stimulates PWM pulsed immunoglobulin and IFN-gamma secretion by human duodenal immunocompetent cells. These results support the hypothesis of local neuropeptidergic-immune interactions.