Immunomodulation by OK-432 and calcitonin gene-related peptide (CGRP) of nitric oxide synthase (NOS) and IL-1 beta gene expression and of HSV-1 pathogenicity in mouse skin Langerhans cells (LC).

The effect of HSV-1 infection in the epidermis on the expression of genes for nitric oxide synthase (NOS) and interleukin-1 beta (IL-1 beta), and the ability of OK-432 to alter this effect were studied. The genes for NOS and IL-1 beta are normally expressed in Langerhans cells as well as in keratinocytes. Neither administration of OK-432 nor infection with HSV-1 abrogates this gene expression. Calcitonin gene-related peptide (CGRP) can inhibit the ability of macrophages and Langerhans cells to act as antigen-presenting cells. The effect of treatment with CGRP on mouse footpads and subsequent infection with HSV-1 was studied and compared with the effects observed after treatment with a specific antagonist for CGRP. Viral DNA was detected in adrenal gland samples of mice treated with the virus only and of mice treated with either CGRP-(1-37) or its antagonist prior to injection of the virus. In spinal cord samples, viral DNA was only detected when mice were treated with the virus or the CGRP antagonist. CGRP-(1-37) at physiological concentrations does not enable HSV-1 injected into mouse footpad skin to reach tissues which are normally resistant.