Neonatal Listeria monocytogenes infection is refractory to interferon.
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.
Bortolussi
R
R
Department of Pediatrics, Dalhousie University, Halifax, Canada.
Burbridge
S
S
Durnford
P
P
Schellekens
H
H
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
D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons