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

Recently, we have demonstrated a substance P (SP)-dependent modulation of in vitro IgM and interferon-γ (IFN-γ) secretion by human peripheral blood mononuclear cells, as well as lymphokine activities in supernatants of cultured duodenal mucosa. Therefore we investigated other local immuno-regulatory effects of SP. Duodenal biopsies of 7 healthy subjects were cultured with Pokeweed mitogen (PWM, 1 μg/ml) for 4 days at 37°C in 1 ml medium each. SP was added in concentrations ranging from 10^-12M to 10^-6M on day 1. Fresh media with fresh PWM were added every day. IgG, IgM, IgA (ELISA) and IFN-γ (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^-6M and 10^-12M SP increased secretion of all immunoglobulin isotypes. Compared to controls, 10^-6M and 10^-12M 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 (α = 0.02 for both isotypes at 10^-6M). 10¹²M to 10^-6 M SP led to a significant dose-dependent increase in IFN-γ 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-γ secretion by human duodenal immunocompetent cells. These results support the hypothesis of local neuropeptidergic-immune interactions.