Effect of neuropeptides (SP and CGRP) on antigen presentation by macrophages

There is increasing evidence that neuropeptides regulate various functions of immune cells, including macrophages, which have functional receptors for neuropeptides. We have studied the effects of substance P (SP) and calcitonin gene-related peptide (CGRP) on the presentation of herpes simplex virus type-one (HSV-1) antigens by mouse peritoneal macrophages. Macrophages were treated with live or heat-killed virus in the presence or absence of one or both neuropeptides, then fixed. In vitro proliferation of lymphocytes, derived from intranasally immunized mice, was used to assess antigen presentation by the macrophages. Lymphocytes derived from cervical lymph nodes exhibited a greater proliferative response to heat-killed viral antigens than did lymphocytes derived from spleen. Macrophages treated with live virus did not induce lymphocyte proliferation in the immunized mice, but those treated with heat-killed viral particles did. When macrophages were treated with heat-killed virus in the presence of CGRP, the lymphocyte proliferative response was decreased; however, the effects of SP and SP + CGRP were not statistically significant. The results of interleukin-2 production were in accordance with proliferation assays. These findings suggest that neuropeptides regulate immune responses partly through their effects on macrophage function, including antigen presentation.