Release of alpha-melanocyte-stimulating hormone from rat splenocytes in vitro is dependent on protein synthesis

The pro-opiomelanocortin (POMC) peptide product alpha-melanocyte-stimulating hormone (alpha-MSH) has a variety of anti-inflammatory effects within the immune system. Using an antiserum specific for alpha-MSH, we have now demonstrated for the first time that this peptide is secreted from splenocytes. Basal secretion of alpha-MSH from the spleen in vitro was some 300-fold less than that detected from the neurointermediate lobe. Secretion of alpha-MSH from the spleen was increased 5-fold in the presence of puromycin, indicating that splenocyte alpha-MSH secretion is under the regulation of a product of endogenous protein synthesis. ACTH and beta-endorphin were also released from splenocytes in vitro, but their release was not affected by incubation with puromycin. Secretion of the POMC peptides from splenocytes or NIL was not affected by corticosterone. These data show that the many anti-inflammatory effects within the immune system ascribed to alpha-MSH may actually be mediated through paracrine effects of immune alpha-MSH.