Polyriboinosinic:polyribocytidylic acid enhances rabbit slow-wave sleep

Abstract

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.