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

Abstract:

: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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

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

doi

10.1203/00006450-200210000-00005

subject

Has Abstract

pub_date

2002-10-01 00:00:00

pages

481-90

issue

4

eissn

0031-3998

issn

1530-0447

journal_volume

52

pub_type

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