Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats

Substance P (SP) plays a major role in the regulation of the interaction be tween immune and nervous systems. SP administration stimulates Con A-induce d proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 prod uction and expression of activation antigens such as IL-2 receptor or chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5(+) and CD4(+) T lymphocytes in the peripheral blood of c apsaicin-treated rats. Concomitant administration of SP with the non-peptid e Neurokinin-l receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 produ ction as well as of CD4(+) CD25(+) and CD4(+) RT1B(+) T cell numbers in nor mal and capsaicin-treated rats. SR 140333 also blocked the increased percen tage of peripheral blood CD4(+) T cells induced by SP in capsaicin-treated rats. (C) 1999 Elsevier Science B.V. All rights reserved.