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Am J Physiol Regul Integr Comp Physiol 255: R748-R755, 1988;
0363-6119/88 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 255, Issue 5 748-R755, Copyright © 1988 by American Physiological Society

ARTICLES

Polyriboinosinic:polyribocytidylic acid enhances rabbit slow-wave sleep

J. M. Krueger, J. A. Majde, C. M. Blatteis, J. Endsley, R. A. Ahokas and A. B. Cady
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.

Drowsiness and fever are common symptoms of many viral diseases. It has been postulated that double-stranded RNA (dsRNA) produced during viral replication may cause these symptoms by direct toxic effects or by inducing interferon (IFN) or other cytokine production. Polyriboinosinic:polyribocytidylic acid (poly I:C), a pyrogenic and IFN-inducing synthetic dsRNA, and polyriboadenylic:polyribouridylic acid (poly A:U), a less effective pyrogen and IFN-inducing substance, were used as models of viral dsRNA to further characterize the physiological response to dsRNA. Poly I:C was injected either intravenously or intracerebroventricularly into rabbits, and electroencephalograph, body movement, and brain temperature were monitored over the next 6 h; blood samples were taken 24 h postinjection. Poly I:C increased slow-wave sleep duration, suppressed rapid-eye-movement sleep, and induced fever but failed to raise plasma Cu. Dose-dependent responses occurred after intravenous or intracerebroventricular injections; minimal effective doses were 0.3 micrograms/kg (iv) and 1.0 ng (icv). Poly A:U failed to alter the sleep or temperature parameters measured. Responses elicited by poly I:C were distinct from those elicited by bacterial products, e.g., endotoxin enhances plasma Cu levels, thus implying different mechanisms. We conclude that poly I:C enhances slow-wave sleep and body temperature without provoking the acute-phase rise in plasma Cu. These effects may be initiated through an IFN-mediated process.


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M.-E. Fortier, S. Kent, H. Ashdown, S. Poole, P. Boksa, and G. N. Luheshi
The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2004; 287(4): R759 - R766.
[Abstract] [Full Text] [PDF]


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