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Pediatric Research 52:481-490 (2002)
© 2002 International Pediatric Research Foundation, Inc.
DOI: 10.1203/01.PDR.0000028250.96650.D7
 

Synergistic Effect of Influenza A Virus on Endotoxin-Induced Mortality in Rat Pups: A Potential Model for Sudden Infant Death Syndrome

JANE BLOOD-SIEGFRIED, ABRAHAM NYSKA, HOLLY LIEDER, MIJEOM JOE, LIBIA VEGA, RACHEL PATTERSON and DORI GERMOLEC

Environmental Immunology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, U.S.A. [J.B.-S., A.N., H.L., L.V., R.P., D.G.]; Duke University School of Nursing, Durham. North Carolina 27707, U.S.A. [J.B.-S., H.L., M.J.]; and CINVESTAV, Farmacobiología, Sección Externa de Toxicología, Zacateneo, Mexico D. F. 07360 [L.V.]

Correspondence: Jane Blood-Siegfried, D.N.Sc., C.P.N.P., Duke University, School of Nursing, Box 3322, Durham, NC 27710, U.S.A.; e-mail blood002@mc.duke.edu

Sudden infant death syndrome is the most common cause of postneonatal infant mortality in the developed world. It is a diagnosis of exclusion with peak age of incidence between 2 and 6 mo. Fifty to 63% of these infants have a preexisting upper respiratory tract infection before death. We hypothesized that the immature immune system may be altered by a primary infection, preventing a protective response after secondary challenge. To mimic dual infection, we used a nonlethal strain of a rat-adapted influenza A virus and a sublethal dose of endotoxin to establish a model that results in pathology and death in 12-d-old rat pups similar to that seen in infants dying of sudden infant death syndrome. Mortality only occurred when specific criteria such as timing between infectious insults and developmental age of the pup were met. Results suggest that mortality is caused by a rapid systemic shock event rather than lung-specific damage. Gross pathologic findings such as lung petechiae and liquid blood around the heart on necropsy were consistent with those seen in infants dying of sudden infant death syndrome. Histopathologic lesions including subendocardial hemorrhage and mild cortical thymocyte necrosis were found with greater severity and frequency in dually challenged animals. Macrophage subpopulation in rat-adapted influenza A virus-inoculated animals was significantly elevated in the spleen at the time of death. Our model suggests that the developing immune system can be primed to respond in an exaggerated way to a second immune challenge resulting in unexpected death.

Abbreviations:
BALF, bronchoalveolar lavage fluid
H&E, hematoxylin and eosin
iNOS, inducible nitric oxide synthase
IFN-, interferon-
NO, nitric oxide
PFU, plaque-forming unit
RBC, red blood cells
TNF-, tumor necrosis factor-
SIDS, sudden infant death syndrome
RAIV, rat adapted influenza A virus

Copyright © 2002 by the International Pediatric Research Foundation.

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