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 t o shock-inducing bacterial products or proinflammatory cytokines (or b oth). Mice of different ages mere inoculated with various doses of lip opolysaccharide (LPS), superantigenic staphylococcal enterotoxin B (SE B), or recombinant tumor necrosis factor-alpha (rTNF-alpha), alone or in combination with the sensitizing agent D-galactosamine, Neonatal mi ce were markedly more susceptible to LPS-induced lethality but more re sistant to SEE 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 SEE correlated directly wit h plasma TNF-alpha bat not IFN-gamma levels, which was confirmed by TN F-alpha and IFN-gamma blockade experiments, These data document marked age-related differences in the pathophysiology of septic shock and su ggest that IFN-gamma is not an obligatory mediator of either LPS- or S EB-induced lethality in neonates.