A substance p agonist acts as an adjuvant to promote hapten-specific skin immunity

Because substance p (SP) has been reported to be released from cutaneous se nsory nerve endings after hapten application, we determined whether SP part icipates in contact hypersensitivity (CH) induction by using a SP agonist, GR73632 or delta-Aminovaleryl [Pro(9), N-Me-Leu(10)] -substance P7-11 and a SP antagonist, spantide I. When injected intradermally, SP agonist enhance d CH induced by conventional, but not optimal, sensitizing doses of hapten. By contrast, SP antagonist inhibited the induction of CH by optimal sensit izing doses of hapten. Moreover, SP agonist promoted CH induction and preve nted tolerance when hapten was painted on skin exposed to acute, low-dose u ltraviolet-B radiation. Intradermally injected SP agonist altered neither t he density nor the morphology of epidermal Langerhans cells, implying that SP agonist enhanced the generation of hapten-specific immunogenic signals f rom the dermis. It is proposed that SP is a natural "adjuvant" that promote s the induction of CH within normal skin. Although exogenous SP agonist can prevent impaired CH and tolerance after ultraviolet-B radiation, the susce ptibility of native SP to local neuropeptidases renders the neuropeptide un able to prevent the deleterious effects of ultraviolet-B radiation on cutan eous immunity.