NEUROPEPTIDES ARE POTENT MODULATORS OF HUMAN IN-VITRO IMMUNOGLOBULIN-E SYNTHESIS

We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enha nced or inhibited IgE synthesis in a culture system where IgE synthesi s was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antib ody in peripheral blood mononuclear cells. Similar effects on IgE synt hesis were observed by adding ACTH-related peptides, e.g. corticotropi n-releasing factor (CRF), the inducer of ACTH, or a-melanocyte stimula ting hormone (a-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not a ct directly on either B or T cells as there was no influence on IgE sy nthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings sugges t that ACTH and the related peptides CRF and alpha-MSH can influence t he microenvironment modulating an IL-4 and anti-CD40 monoclonal antibo dy driven class switching to IgE via accessory cells.