TUMOR-NECROSIS-FACTOR-ALPHA IN RESPONSE TO ENDOTOXIN ADMINISTRATION IN THE PREGNANT GUINEA-PIG

OBJECTIVE: Our purpose was to test the hypothesis that an intramuscula r endotoxin challenge induces production of tumor necrosis factor-alph a in the pregnant guinea pig and to investigate some of the metabolic effects. STUDY DESIGN: Twelve randomly selected guinea pigs at 33 days ' gestation with a sampling catheter in the carotid artery received an intramuscular injection of a solution of endotoxin isolated from Bact eroides fragilis (n = 6) or of solvent alone (n = 6). Plasma values of tumor necrosis factor-alpha, hematocrit, and 6-keto-prostaglandin F-1 alpha were determined before and several hours after injection. RESUL TS: Tumor necrosis factor-alpha was detected in five of six guinea pig s, but it could not be demonstrated in five or six placebo animals. Th e hematocrit was significantly decreased, and prostaglandin F-1 alpha significantly increased 24 to 48 hours after endotoxin injection. CONC LUSION: In pregnant guinea pigs an intramuscular endotoxin challenge i nduces the release of tumor necrosis factor-alpha, followed by a reduc ed hematocrit and an increased prostacyclin concentration. These effec ts could be involved in the pathogenesis of endotoxin-induced fetal gr owth retardation.