The pituitary-adrenal axis is known to be stimulated during the acute-phase response. As cytokines play a central role in mediating the constellation of host response occurring during the acute-phase response it was of interest to assess the ability of cytokines to stimulate ACTH secretion from normal pituitary cells in culture. We used human recombinant interleukin-1β and -α (hrlL1β, hrlL1α) and human recombinant tumor necrosis factor α (hrTNFα) to analyze the ability of these cytokines to induce ACTH secretion from normal rat anterior pituitary cells in culture. We also investigated the possible roles of prostaglandin E2
) and cAMP in the cellular transduction mechanism. After 3 days of incubation primary cultures of rat anterior pituitary cells were stimulated for 24 h with either hrlL1β, hrlL1α or hrTNFα alone or with the addition of dexamethasone or indomethacin. The culture media were analyzed for ACTH, PGE2
and cAMP content. At doses ranging from 0.03 to 30 nM, hrlL1β stimulated the release of ACTH and PGE2
in a dose-dependent manner. In contrast, at doses ranging from 3 to 60 nM, hrTNFα was unable to stimulate ACTH secretion although it stimulated PGE2
synthesis. Time-course experiments demonstrated that hrlL1β (3 nM
) stimulates ACTH production over a period of 8, 16 and 24 h, but not after a period of 4 h. In these experiments, hrlL1β failed to cause any change in the secretions of growth hormone and luteinizing hormone. In hrlL1β-stimulated cells, indomethacin (10 mM
) completely inhibited PGE2
production without significantly affecting ACTH release, whereas dexamethasone (50 nM), which also inhibited PGE2
production, partially inhibited ACTH secretion. Finally indomethacin blocked the hrlL1β-induced cAMP accumulation obtained after 24 h, without significantly affecting hrlL1β-induced ACTH release. The results obtained with hrlL1α were similar to those obtained with hrlL1β. In conclusion, although hrlL1β, hrlL1α and hrTNFα stimulate PGE2
synthesis, only hrlL1β and hrlL1α stimulate ACTH release from normal rat anterior pituitary cells in culture. The stimulation is partially inhibited by dexamethasone and the cellular transduction mechanism involved in this ACTH release does not depend on PGE2
or cAMP. These results confirm the interaction between the endocrine and the immune systems. They suggest that the monokine-induced stimulation of the pituitary-adrenal axis may represent a potent negative feedback mechanism through which the immune system avoids an overshoot of the inflammatory and febrile effect stimulated during the acute-phase response.
Dr. R.C. Gaillard, MD, Clinique Médicale, University Hospital, CH-1211 Geneva 4 (Switzerland)
Received: June 15, 1987
Accepted after revision: January 22, 1988
Published online: April 02, 2008
Number of Print Pages : 7
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 48, No. 2, Year 1988 (Cover Date: 1988)
Journal Editor: Millar R.P. (Edinburgh)
ISSN: 0028–3835 (Print), eISSN: 1423–0194 (Online)
For additional information: http://www.karger.com/NEN
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