title: Neonatal Listeria monocytogenes infection is refractory to interferon.
abstract: Despite aggressive treatment, early onset neonatal Listeria monocytogenes infection continues to have high morbidity and mortality. We recently showed that pretreatment of newborn L. monocytogenes-infected rats with interferon (IFN)-alpha/beta or recombinant rat IFN-gamma dramatically improves survival. However, in the present experiment, when newborn rats were treated with IFN-alpha/beta or recombinant rat IFN-gamma after intraperitoneal injection with Listeria there was no benefit. Because most deaths occurred at or before 3 d in this animal model, we reasoned that the effect of interferon may be evident if animals survived longer. To accomplish this and test this hypothesis, ampicillin (20 mg/kg/d) was given 48 h after bacterial challenge. When ampicillin-treated Listeria-infected rats were randomized to receive PBS, IFN-alpha/beta, or recombinant rat IFN-gamma, mortality rates were 79, 76, and 69%, respectively (p greater than 0.05 versus PBS). Animals treated in a similar fashion after a lower bacterial inoculum (25% lethal dose) were killed 5 d after bacterial challenge. Bacterial concentrations in the spleen were higher for IFN-treated animals than controls. We conclude that no direct benefit of IFN is found if it is given after bacterial infection has been established.
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Bortolussi
authors.forename: S
authors.initials: S
authors.lastname: Burbridge
authors.forename: P
authors.initials: P
authors.lastname: Durnford
authors.forename: H
authors.initials: H
authors.lastname: Schellekens
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004351:Drug Resistance; D007370:Interferon Type I / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D008088:Listeriosis / Q000517:prevention & control / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons