Synergistic effect of influenza a virus on endotoxin-induced mortality in rat pups: a potential model for sudden infant death syndrome.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Blood-Siegfried, J; Nyska, A; Lieder, H; Joe, M; Vega, L; Patterson, R; Germolec, D

Published Date

  • October 2002

Published In

Volume / Issue

  • 52 / 4

Start / End Page

  • 481 - 490

PubMed ID

  • 12357040

Electronic International Standard Serial Number (EISSN)

  • 1530-0447

International Standard Serial Number (ISSN)

  • 0031-3998

Digital Object Identifier (DOI)

  • 10.1203/00006450-200210000-00005


  • eng