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Molecular Mechanisms of Actions of Interleukin-6 on the Brain, with Special Reference to Serotonin and the Hypothalamo-Pituitary-Adrenocortical Axis

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Abstract

Biological activities of the multifunctional cytokine, interleukin-6 (IL-6) include stimulation of B cell proliferation, immunoglobulin production, and initiation of the acute-phase response. IL-6 affects the CNS in that it activates the hypothalamo-pituitary-adrenocortical (HPA) axis and increases brain tryptophan and serotonin metabolism. IL-6 has been proposed as an important mediator of interaction between the neuroendocrine and immune systems. The peripheral and central effects of IL-6 are presumably mediated through its membrane receptor (IL-6R). IL-6, IL-6R and their respective mRNAs have been detected in several brain regions. Although the functions of cytokines overlap considerably, each displays its own characteristic properties. Expression of IL-6 in the brain has been observed in several CNS disorders, some of which have been associated with disorders of serotonin metabolism. It is proposed that interactions between IL-6 and brain serotonin is a complex process which involves corticotropin-releasing factor (CRF) and opioid peptides. It is likely that the molecular mechanisms underlying the actions of IL-6 on the HPA axis and its other brain functions involve the integrated effects of glutamate, Ca2+, 3′,5′-cyclic AMP, protein kinase C, and other metabolic pathways.

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  1. Nina Barkhudaryan

    Present address: Institute of Biochemistry NAS RA, Sevak str. 5/1, 375014, Yerevan, Armenia

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  1. Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, Louisiana, 71130-3932

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Barkhudaryan, N., Dunn, A.J. Molecular Mechanisms of Actions of Interleukin-6 on the Brain, with Special Reference to Serotonin and the Hypothalamo-Pituitary-Adrenocortical Axis. Neurochem Res 24, 1169–1180 (1999). https://doi.org/10.1023/A:1020720722209

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