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 or 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.

PROCEDURE

Cells were cultured for 3 to 5 days, then were treated with oIL for variable periods. Cells were washed and treated with the hypothalamic peptides corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) or both. Medium bathing the cells was collected and assayed for ACTH concentration.

RESULTS

Ovine IL-1 alpha and oIL-1 beta, but 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 not 18 or 24 hours of exposure. Treatment with oIL-1 did not affect basal release of ACTH. Exposure of cells to phorbol 12-myristate 13-acetate or calphostin C before treatment with oIL-1 beta inhibited the ability of the cytokine to augment ACTH release, suggesting a role for protein kinase C in the process.

CONCLUSIONS

Local concentration of oIL-1 in the sheep pituitary gland may have an important role in determining secretion of ACTH in response to CRH or AVP or both from the hypothalamus.

CLINICAL RELEVANCE

The hypothalamic-pituitary-adrenocortical axis may be activated after immune challenge. The cytokine oIL-1 has been implicated as an important mediator in this process. The pituitary gland may be an important target for this effect.