Human immunodeficiency virus envelope glycopotein 120 alters sleep
and induces cytokine mrna expression in rats.
Opp, Mark R., Peter L. Rady, Thomas K. Hughes, Jr., Patrick Cadet,
Stephen K. Tyring, and Eric M. Smith.
Departments of Psychiatry and Behavioral Sciences, and Microbiology
and Immunology, University of Texas Medical Branch, Galveston, TX
USA
APStracts 2:0314R, 1995.
Sleep is altered during the course of viral infection, including that
in which the human immunodeficiency virus (HIV) is the etiologic
agent. Alterations in the sleep of HIV-infected individuals occur
early in the course of infection, prior to the onset of AIDS. The
mechanisms for such alterations in sleep are not known. The HIV
envelope glycoprotein (gp) 120 induces the synthesis and secretion of
cytokines that enhance (e.g. interleukin [IL]-1, tumor necrosis
factor) and suppress (e.g. IL-10, IL-1 receptor antagonist) sleep. We
used a well-defined rat model to test the hypothesis that the HIV
gp120 alters sleep. Recombinant HIV-1IIIB gp120 was injected
intracerebroventricularly (ICV; 20 - 500 ng) into rats prior to dark
onset. Sleep-wake behavior was not altered following the 20 ng dose,
whereas both non-rapid eye movement sleep (NREMS) and REMS were
initially enhanced and subsequently suppressed after the 100 ng dose.
NREMS was enhanced for eight hours after the 500 ng dose; REMS was
not affected by this dose. Brain temperature was not altered by any
of the gp120 doses used in this study. In addition, mRNA expression
for IL-1[beta] and IL-10 was induced in the hypothalamus by gp120;
this brain region is crucial for the regulation of sleep. These new
data support the hypothesis that altered cytokine concentrations
within the central nervous system play a pivotal role in the complex
alterations in sleep observed during HIV infection.
Received 6 July 1995; accepted in final form 7 November 1995.
APS Manuscript Number R425-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95