Protective Effect ofLow-Dose Interferon Against Neonatal MurineCytomegalovirus Infection

Micewere injected with10or 5,000 reference units ofinterferon intraperitoneally orsubcutaneously within 24hofbirth andreinoculated intraperitoneally 24h later with200plaque-forming units ofmurinecytomegalovirus. Mock interferon andvirus diluent were thecontrol inocula. Infection ofmockinterferontreated miceresulted insignificant retardation ofgrowth, accompanied bytissue injury andadepressed blastogenic responseofsplenic lymphocytes. Prophylactic administration ofinterferon prevented growth retardation andresulted inlower tissue viral titers anddiminished injurious effects ofthevirus. Intraperitoneal inoculation ofinterferon was more protective thanwas subcutaneous, and10U ofinterferon was often as effective as 5,000 U.Accelerated maturation and enhanced activity oflymphoid elements were observed histologically inspleens andlymphnodesofinterferon-treated mice; supportive ofthese findings was the greater incorporation of[3H]thymidine ofsplenocytes frominterferon-treated mice. Theprotective effect ofinterferon may,therefore, beduetostimulation or accelerated maturation ofcellular immunefunctions. Immunologically immature andcompromised hosts aremostatrisk ofsuffering tissue injury duetocytomegalovirus (CMV)infection. Congenital infections usually produce theseverest sequelae (15, 23,27). Natal infections occur more commonly, butareusually asymptomatic (9, 14, 18), although long-term excretion ofvirus and protracted pneumonitis havebeenreported (22, 28). Infections ofimmunocompetent adults are almost always asymptomatic, andwhenaclinicalsyndrome results, suchasCMV mononucleosis, theprognosis isgood. Thus, stimulating or accelerating thematuration ofimmunefunctions maybeuseful inmodulating theeffects of natal CMV infections. Although beneficial effects ofinterferon (IF) asanantiviral therapeutic agent insymptomatic CMV patients havenotbeendemonstrated (1, 7),theencouraging prophylactic useofIFin transplant patients (3) suggests thatCMV infections maybeamenable tothis treatment. However, large quantities ofhigh-titered preparations mustbeusedtodemonstrate theantiviral properties ofIF.Thepotential sideeffects of large doses ofIFhavenotbeenadequately defined. Innewbornmice, multiple injections of high-titered IFmaycauseglomerulonephritis anddeath(10). Furthermore, large doses ofIF arelikely tobeimmunosuppressive, whereas low