Hypothalamic releasing hormones mediating the effects of interleukin‐1 on sleep

Abstract

There is a substantial literature describing the interactions between the endocrine and immune systems. Although such interactions are less well known within the brain, one major brain function altered during inflammation and infection and by several endocrine hormones is sleep. Pathological disturbances, be they inflammation, infectious disease, and/or sleep deprivation, result in altered hypothalamus-pituitary function and cytokine metabolism. In respect to hormone secretion from the pituitary, cytokines are now recognized to play an important role in modulating the neuroendocrine system. Changes in sleep provide a useful illustration of the interactions between cytokines and the hypothalamus-pituitary axis. Evidence linking interleukin-I (IL-I ) to growth hormone releasing hormone and to corticotropin releasing hormone in regard to their effects on sleep is reviewed. c 1993 WiIey-Liss, Inc.Key words: cytokines, growth hormone releasing hormone, corticotropin releasing hormone, endocrine regulation, neuroendocrineThe host's initial response to infections is a nonspecific defense reaction called the acute phase response. The acute phase response promotes specific responses to the infectious agents mediated by cellular and humoral immune mechanisms. The acute phase response does this by several ways: the immune system is stimulated; an environment is provided which enhances the effectiveness of the specific immune response and at the same time is not optimal for the replication and spreading of the infectious agents; and the behavior and responsiveness to stimuli of the individual are modified in such a way that the exposure to further environmental challenges is reduced. These changes require substantial alterations in almost all functions of the body. The clinical manifestations of these alterations are the leading symptoms of sickness which are easily recognized by everybody: fever, somnolence, social withdrawal, reduced apetite, muscle pain, etc. Laboratory readings are also abnormal; changes are recorded in plasma proteins, in the number Received May 17, 1993; accepted July 16, 1993. Address reprint requests to James M. Krueger, University of Tennessee, Department of Physiology and Biophysics, 894 Union Avenue, Memphis, TN 38163. and percentage distribution of leukocytes, and in concentrations of various hormones: red blood cell sedimentation increases, and the basal metabolic rate is elevated [ll. An acute phase response, exaggerated in magnitude or prolonged, is detrimental to the individual. However, negative feedback mechanisms are also activated which attenuate various aspects of the functional changes and abolish the response when the infection is eliminated.Much information has accumulated within the past few years indicating that most, if not all, aspects of the acute phase response are driven by a complex array of cytokines in association with classical stress hormones [21. Most cytokines were first identified as immunocyte products involved in the amplification, coordination, and regulatio...

Inflammation, Sleep, Obesity and Cardiovascular Disease.

“…Immune molecules alter sleep architecture and sleep deprivation alters neuroendocrine and immune response [58]. Furthermore, immune system activation and neuroendocrine responses alter sleep [58].…”

Growth-Hormone-Releasing Hormone Mediates the Sleep-Promoting Activity of Interleukin-1 in Rats

“…Thus, the increased GH release supports the immunomodulatory function of IL1 at the periphery. Enhanced NREMS is also one facet of the acute-phase reaction: the decreased energy expendi ture associated with enhanced NREMS makes it possible that a significant portion of metabolic activity is used for the defense of the organism [37]. Stimulation of GHRH.…”

“…CRH inhibits GH secretion [41,42] in the rat and sleep-related GH release in humans [43] and suppresses sleep in rats [1]. rabbits [44] and humans [43], Suppression of GH secretion [22] and sleep [18] after high doses of IL1 may reflect the activity of the negative feedback, the stimula tion of CRH by IL1 [37].…”

Geschlechtsspezifische Unterschiede der schlafendokrinen Regulation und deren Bedeutung für die Pathophysiologie der Major Depression

“…Die Schlafförderung durch proinflammatorische Zytokine scheint jedoch vor allem bei gering bis mäßig erhöhten Konzentrationen aufzutreten (Lancel et al 1996b;Mullington et al 2000;Pollmächer et al 2002). Hingegen hemmen höhere Konzentrationen NREM Schlaf und fördern die CRH Sekretion (Opp et al 1989;Payne et al 1993 (Dijk 1995;Dijk and Czeisler 1995a;Lancel et al 1992). …”

“…Pro-inflammatorische Zytokine beeinflussen konzentrationsabhängig die schlafendokrine Regulation: So führen niedrige Konzentrationen zu einer Abnahme der Wachzeiten und zu einer Zunahme von Tiefschlaf, während hohe Konzentrationen gegensätzliche Veränderungen bewirken (Lancel et al 1996b;Mullington et al 2000;Opp et al 1989;Payne et al 1993;Pollmächer et al 2002 (Bonaccorso et al 2001;Maes et al 1997;Musselman et al 2001). Auch wurde vermutet, dass es eine Beziehung zwischen einer verstärkten IL-1β Sekretion und der Entwicklung depressiver Symptome gibt (Anisman et al 1999b;Owen et al 2001), wobei insbesondere IL-1β als 'trait marker' vorgeschlagen wurde, der mit einem frühen Krankheitsbeginn und einem chronischen Verlauf assoziiert sein könnte (Anisman et al 1999b Vorstufe des Serotonin, bei (Barkhudaryan and Dunn 1999;Leonard 2001;Maes et al 1994;Song et al 1998).…”