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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)-α/β or recombinant rat IFN-γ dramatically improves survival. However, in the present experiment, when newborn rats were treated with IFN-α/β or recombinant rat IFN-γ 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-traated Listeria-infected rats were randomized to receive PBS, IFN-α/β, or recombinant rat 1FN-γ, mortality rates were 79, 76, and 69%, respectively (p > 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.