ASSOCIATION BETWEEN PROTECTIVE EFFICACY OF ANTIBODIES TO TUMOR-NECROSIS-FACTOR AND SUPPRESSION OF NITRIC-OXIDE PRODUCTION IN NEONATAL RATS WITH FATAL INFECTION

In a rat model of fatal infection caused by Pseudomonas aeruginosa, th e circulating level of nitrite/nitrate (NO2-/NO3-), a good indicator f or nitric oxide production, was remarkably increased after elevation o f circulatory tumor necrosis factor (TNF). Anti-TNF MAb cotreatment wa s shown to blunt hypoglycemia and hyperlacticemia and was associated w ith decreased mortality of septic animals. Moreover, anti-TNF MAb sign ificantly reduced not only plasma TNF but also plasma NO2-/NO3- levels . Dexamethasone had a similar effects, and when anti-TNF MAb was used in combination with dexamethasone, the suppression of nitric oxide pro duction and the protective efficacy were more remarkable compared with therapy with either anti-TNF MAb or dexamethasone alone. Our present data suggested that the protective efficacy of anti-TNF MAb may correl ate with the suppression of nitric oxide production and also with a mo dulation in metabolic abnormalities in the septic newborn rats.