INHIBITION OF THE INDUCTION OF DELAYED-TYPE AND CONTACT HYPERSENSITIVITY BY CALCITONIN-GENE-RELATED PEPTIDE

Calcitonin gene-related peptide (CGRP)-containing nerves are frequentl y associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate poss ible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hy persensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2(a)) was employed to examine induction of DTH by LC. This system requires exposure of epidermal cells (EC) to GM-CSF for in duction of substantial immunity. EC were prepared from CAF(1) mice (H- 2(a/d)) and Thy-1(+) cells deleted. EC were exposed for 16 h to GM-CSF with or without CGRP. EC were then pulsed with tumor-associated Ags ( TAA), washed, and injected s.c, into mice three times at 7-day interva ls for immunization. Mice were challenged for a DTH response by inject ion of a hind footpad with TAA-pulsed EC, and 24-h footpad swelling as sessed. Exposure of EC to CGRP significantly inhibited induction of DT H. To examine the effect of CG RP administered in vivo on induction of immunity, 530 pmol of CGRP or diluent alone was injected intradermall y into the dorsum of the left ear of naive mice 8 h and 3 h before epi cutaneous application of a hapten at the injected site. Mice were chal lenged on the right ear 7 days later and 24 h ear swelling was assesse d. CGRP significantly inhibited the induction of CHS whereas calcitoni n had no effect. Furthermore, when hapten was applied at a site distan t from CGRP administration, no inhibition of CHS was observed, suggest ing that the effect of CGRP is local. These data support the concept t hat CGRP may be an endogenous regulator of immune function and also su ggest the possibility that CGRP or its analogues administered in vivo might have therapeutic utility as immunomodulators.