Corticotropin-releasing hormone differentially modulates the interleukin-1 system according to the level of monocyte activation by endotoxin.
The interleukin-1 (IL-1) system is constituted by IL-1 alpha and IL-1 beta and IL-1 receptor antagonist (IL-1ra) that bind the same IL-1 receptors. Hypothalamic-pituitary-adrenal axis hormones are major mediators of the neuroendocrine control over immune function. Corticotropin-releasing hormone (CRH) is produced in peripheral inflammatory sites; its direct effects on inflammatory cytokine synthesis, however, remain unclear. We have studied the effects of CRH (0.1-100 nM) on IL-1 beta and IL-1ra expression by human peripheral monocytes in culture activated with different doses of lipopolysaccharide (LPS). In the absence of LPS, CRH up-regulated IL-1ra and IL-1 beta messenger RNA expression as well as protein synthesis. No significant changes were observed with low doses of LPS (1 ng/ml). In contrast, in combination with high doses of LPS (1 microgram/ml), CRH caused inhibition of IL-1ra and IL-1 beta transcription and secretion. The CRH effects were blocked by its antagonist alpha-helical CRH and mediated by intracellular cAMP. These data indicate that CRH modulates the IL-1 system; depending on the state of activation of the monocyte, CRH exerts an inhibitory control on the activated cell and a stimulatory action on the resting monocyte.
Paez Pereda
M
M
Instituto de Investigaciones Médicas, Universidad de Buenos Aires, Argentina.
Sauer
J
J
Perez Castro
C
C
Finkielman
S
S
Stalla
G K
GK
Holsboer
F
F
Arzt
E
E
D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP