Neonatal hypersusceptibility to endotoxin correlates with increased tumor necrosis factor production in mice.
Septic shock is a major cause of mortality in neonates. The hypothesis was tested that neonatal age is associated with altered sensitivity to shock-inducing bacterial products or proinflammatory cytokines (or both). Mice of different ages were inoculated with various doses of lipopolysaccharide (LPS), superantigenic staphylococcal enterotoxin B (SEB), or recombinant tumor necrosis factor-alpha (rTNF-alpha), alone or in combination with the sensitizing agent D-galactosamine. Neonatal mice were markedly more susceptible to LPS-induced lethality but more resistant to SEB than were adults (P < .05). Mice of different ages did not differ, however, in their sensitivity to lethal activities of rTNF-alpha. Neonatal susceptibility to LPS and SEB correlated directly with plasma TNF-alpha but not IFN-gamma levels, which was confirmed by TNF-alpha and IFN-gamma blockade experiments. These data document marked age-related differences in the pathophysiology of septic shock and suggest that IFN-gamma is not an obligatory mediator of either LPS- or SEB-induced lethality in neonates.
Cusumano
V
V
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia dell'Universita di Messina, Italy.
Mancuso
G
G
Genovese
F
F
Cuzzola
M
M
Carbone
M
M
Cook
J A
JA
Cochran
J B
JB
Teti
G
G
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004768:Enterotoxins / Q000633:toxicity; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004768:Enterotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma