Involvement of Corticotropin-Releasing Hormone- and Interleukin (IL)-6-Dependent Proopiomelanocortin Induction in the Anterior Pituitary during Hypothalamic-Pituitary-Adrenal Axis Activation by IL-1α

• Published in: Endocrinology (Philadelphia) Vol. 146; no. 12; pp. 5496 - 5502
• Main Authors: Chida, Dai, Imaki, Toshihiro, Suda, Toshihiro, Iwakura, Yoichiro
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2005
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Vertebrates: endocrinology; Endocrine gland; Induction; Cytokine; Central nervous system; Corticotropin releasing factor; Interleukin 1α; Activation; Hypothalamus; Prohormone; Encephalon; Hypothalamic hormone; Adenohypophysis; Interleukin 6; Proopiocortin; Pituitary gland; Hormone releasing factor
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2005-0409

IL-1α/β and IL-6 are endogenous modulator of hypothalamo-pituitary-adrenal axis (HPAA) and are thought to play key roles in immune-neuroendocrine interactions during inflammation. Here, we show IL-1α induced a normal HPAA activation in IL-1α/β knockout (KO) and IL-6 KO mice at 1 h; however, at 6 h HPAA activation was reduced relative to wild-type mice, indicating a role for endogenous IL-1α/β and IL-6 in prolonged HPAA activation. We found that the induction of proopiomelanocortin (POMC) transcript in the anterior pituitary (AP) at 6 h in response to IL-1α was reduced in IL-1α/β KO and IL-6 KO mice, as well as in CRH KO mice, suggesting IL-1α/β, IL-6, and CRH are all required for POMC induction. The induction of CRH transcript in the paraventricular nucleus at 6 h and plasma IL-6 levels, in response to IL-1α, were reduced in IL-1α/β KO mice. Because IL-1α-induced activation of signal transducer and activator of transcription 3 in the AP was also suppressed in IL-6 KO mice, we suggest that plasma IL-6 is first induced by IL-1α, and IL-6 activates signal transducer and activator of transcription 3 in the AP, leading to the induction of POMC in concert with CRH. Our results suggest a role for IL-1α/β in the induction of POMC in the AP through the induction of two independent pathways, CRH and IL-6.