Substance P modulates lymphokine activities in supernatants of cultured human duodenal biopsies.
A duodenal biopsy culture technique was used to investigate the effect of substance P on lymphokine secretion by the human gut associated lymphoid tissue. Duodenal biopsies of 7 healthy volunteers were cultured in 1 ml medium each with Pokeweed mitogen (1 microgram/ml) for 4 days at 37 degrees C. Substance P (SP) was added in concentrations ranging from 10(-12) M to 10(-6) M. Media were changed every day. Interleukin (IL)-1 beta, IL-2 and IL-2-receptor activities were determined by means of specific ELISAs. Values were referred to 5 mg biopsy weight and expressed as per cent change of basal Pokeweed mitogen-pulsed supernatant activities. 10(-8) M and 10(-6) M SP led to a decrease of IL-1 beta activity (78 +/- 13.9% and 62.8 +/- 17.1%, respectively, alpha = 0.01 each). In contrast, 10(-8) and 10(-10) M SP showed an increase in IL-2 activity up to 182.9 +/- 94.5% and 295.6 +/- 144.7%, respectively. 10(-6) M and 10(-8) M SP enhanced IL-2 receptor activities by 81.5 +/- 70% and 40.9 +/- 11.8%, respectively (alpha = 0.05). The present data demonstrate for the first time distinct SP-mediated effects on lymphokine activities in supernatants of cultured human duodenal biopsies.