ENHANCEMENT OF SECRETAGOGUE-INDUCED ADRENOCORTICOTROPIC HORMONE-RELEASE FROM CULTURED SHEEP ANTERIOR-PITUITARY-CELLS BY RECOMBINANT OVINE INTERLEUKIN-1

Objective-To determine whether recombinant ovine interleukin (oIL)-1 o r oIL-2 alters basal or hypothalamic peptide-induced secretion of ACTH from cultured sheep pituitary cells. Animals-The pituitary gland was collected from castrated male sheep ranging from 0.5 to 1 year old. Pr ocedure-Cells were cultured for 3 to 5 days, then were treated with oI L for variable periods. Cells were washed and treated with the hypotha lamic peptides corticotropin-releasing hormone (CRH) or arginine vasop ressin (AVP) or both. Medium bathing the cells was collected and assay ed for ACTH concentration. Results-Ovine IL-1 alpha and oIL-1 beta, bu t not oIL-2, increased the amount of ACTH released in response to CRH, AVP, and CRH and AVP combined. Both oIL were effective after 3, but n ot 18 or 24 hours of exposure. Treatment with oIL-1 did not affect bas al release of ACTH. Exposure of cells to phorbol 12-myristate 13-aceta te or calphostin C before treatment with oIL-1 beta inhibited the abil ity of the cytokine to augment ACTH release, suggesting a role for pro tein kinase C in the process. Conclusions-Local concentration of oIL-1 in the sheep pituitary gland may have an important role in determinin g secretion of ACTH in response to CRH or AVP or both from the hypotha lamus. Clinical Relevance-The hypothalamic-pituitary-adrenocortical ax is may be activated after immune challenge. The cytokine oIL-1 has bee n implicated as an important mediator in this process. The pituitary g land may be an important target for this effect.