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      Central Interleukin-1 β Suppresses the Nocturnal Secretion of Melatonin

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          Abstract

          In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1 β in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1 β on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1 β (50  µg/animal) suppressed ( P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased ( P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1 β also inhibited ( P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1 β to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1 β in the aetiology of disruptions in melatonin secretion.

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          Most cited references65

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          Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones.

          The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.
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            IL-1 receptor 2 (IL-1R2) and its role in immune regulation.

            The cytokine IL-1 is critical to the pathogenesis of a variety of human conditions and diseases. Unlike most other cytokines, IL-1 is counterbalanced by two endogenous inhibitors. The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra. In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1. While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling. IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP). Additionally, IL-1R2 exists in both a membrane bound and soluble form (sIL-1R2) that has biological properties similar to both a decoy receptor and a binding protein. Thus far, IL-1R2 has been implicated in arthritis, endometriosis, organ transplantation, sepsis/sickness behavior, diabetes, atherosclerosis, autoimmune inner ear disease (AIED), Alzheimer's disease and ulcerative colitis. In this review, we will detail the functional properties of IL-1R2 and examine its role in human disease. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Interleukin-1, neuroinflammation, and Alzheimer's disease.

              Interleukin-1 (IL-1)-1) is a pluripotent immunomodulatory cytokine that has an initiating role in cellular and humoral immunity in the periphery. Il-1 is overexpressed in Alzheimer brain, and this overexpression is directly related to plaque formation and progression, nonsensical growth of dystrophic neurites, and neuronal overexpression of acetylcholinesterase. IL-1 has a number of actions relevant to Alzheimer's disease, including excessive expression of neuronal Abeta precursor protein and other plaque-associated proteins, and induction of astrocyte activation and astrocytic overexpression of S100B. These latter events may be related to the overgrowth of dystrophic neurites in neuritic plaques, a necessary event for conversion of diffuse Abeta deposits into the neuritic amyloid plaques diagnostic of Alzheimer's disease. Four new genetic studies underscore the relevance of IL-1 to Alzheimer pathogenesis, showing that homozygosity of a specific polymorphism in the IL-1A gene at least triples Alzheimer risk, especially for an earlier age of onset and in combination with homozygosity for another polymorphism in the IL-1B gene.
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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2016
                26 April 2016
                : 2016
                : 2589483
                Affiliations
                1The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 Street, 05-110 Jabłonna, Poland
                2The Academy of Cosmetics and Health Care, 13 Podwale Street, 00-252 Warsaw, Poland
                Author notes

                Academic Editor: Yona Keisari

                Article
                10.1155/2016/2589483
                4861797
                27212805
                0fac27a8-b15e-4dd9-873e-f7b2d8a93d05
                Copyright © 2016 A. P. Herman et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2016
                : 10 April 2016
                Categories
                Research Article

                Immunology
                Immunology

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