Substance P enhances interferon-gamma production by human peripheral blood mononuclear cells.

Substance P (SP), a neuropeptide widely distributed in the organism, has been shown to stimulate lymphocyte proliferation and immunoglobulin synthesis. However, the effect of SP on specific lymphokines is unknown. Therefore we investigated the influence of SP on mitogen-induced interferon-gamma (IFN-gamma) production in vitro. Peripheral blood mononuclear cells (PBMC) of healthy donors were isolated by density gradient centrifugation and cultured in supplemented RPMI 1640 medium with phytohemagglutinin (PHA) or pokeweed mitogen (PWM), 0.125 and 0.25 mg/liter each, and varying concentrations of SP (10(-12) to 10(-6) M). After 24 and 48 h, IFN-gamma was measured in the supernatant using radioimmunoassay. Results were expressed as percent change of controls. SP alone had no relevant IFN-gamma inducing properties. It enhanced the IFN-gamma production of PWM-stimulated cells significantly up to 18%. The maximal effect was observed at 10(-8) M. PHA-stimulated cells also increased their IFN-gamma production after addition of SP. However, due to great interindividual variations this effect did not attain statistical significance. Stimulation of IFN-gamma production by SP might be of physiological importance, since the effect was seen at concentrations comparable to those found in the body. Our data lend further support to the immunoregulatory functions of SP.