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Interferon induces sleep and other CNS responses in mice recovering from hexobarbital anesthesia
1Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis 55455.
Immediately after recovery from hexobarbital anesthesia, mice were injected intraperitoneally with one of the following interferons: natural mouse alpha/beta, recombinant mouse (rmouse gamma IFN-A) or human alpha A, alpha D, alpha AD interferon (rHu alpha IFN-A, rHu alpha IFN-D, rHu alpha IFN-AD). All of these interferons, except rHu alpha IFN-A induced unconsciousness ("sleep"); all produced stimulatory effects that mimicked those produced by morphine in the mouse. Quantification of the duration of sleep, induced by rmouse gamma IFN, was investigated and found to be dose-related. Only 3 of the 5 interferons (mouse alpha/beta IFN; rmouse gamma IFN, rHu alpha IFN-AD) possesses antiviral activity and depresses the cytochrome P-450 system in the mouse, yet all 5 of the interferons produced CNS effects. This partition of effects, together with the very short latency of the interferon-induced CNS effects, shows that the CNS effects were mechanistically independent of the anti-viral and anti-cytochrome P-450 effects. This disparity of the actions of the interferons suggests the possibility that selected morphine antagonists could be used to counter some of the dose-limiting CNS effects of the large doses of interferons used in clinical situations.
Immediately after recovery from hexobarbital anesthesia, mice were injected intraperitoneally with one of the following interferons: natural mouse alpha/beta, recombinant mouse (rmouse gamma IFN-A) or human alpha A, alpha D, alpha AD interferon (rHu alpha IFN-A, rHu alpha IFN-D, rHu alpha IFN-AD). All of these interferons, except rHu alpha IFN-A induced unconsciousness ("sleep"); all produced stimulatory effects that mimicked those produced by morphine in the mouse. Quantification of the duration of sleep, induced by rmouse gamma IFN, was investigated and found to be dose-related. Only 3 of the 5 interferons (mouse alpha/beta IFN; rmouse gamma IFN, rHu alpha IFN-AD) possesses antiviral activity and depresses the cytochrome P-450 system in the mouse, yet all 5 of the interferons produced CNS effects. This partition of effects, together with the very short latency of the interferon-induced CNS effects, shows that the CNS effects were mechanistically independent of the anti-viral and anti-cytochrome P-450 effects. This disparity of the actions of the interferons suggests the possibility that selected morphine antagonists could be used to counter some of the dose-limiting CNS effects of the large doses of interferons used in clinical situations.