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 β 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)...
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| Autores principales: | , , , , , , |
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| Formato: | JOUR |
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00137227_v136_n12_p5504_Pereda |
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| Sumario: | The interleukin-1 (IL-1) system is constituted by IL-1 alpha and IL-1 β 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 β 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 β 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 μ/ml), CRH caused inhibition of IL-1ra and IL-1 β 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. © 1995 by The Endocrine Society. |
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