Age-related changes in endotoxin sensitivity and the febrile response of newborn rabbits

Thermoregulatory responses to pyrogens in the immediate newborn period have been reported suppressed or undeveloped. In this study we investigated these responses in the newborn rabbit. Endotoxin (Escherichia coli LPS) was injected intraperitoneally in rabbits at different doses on day 0 (day of delivery), 1 or 3 of life, each animal being used only once. Oxygen consumption (VO2) and colonic temperature (Tc) were measured continuously for up to 5 h following endotoxin administration. On all days, a thermogenic response of a similar pattern was seen. At a low dose of endotoxin, there was a monophasic rise in VO2 that reached a peak at 2 h, followed by a plateau phase lasting a further 2-3 h. At an intermediate dose the response was biphasic with an initial smaller peak after 45-60 min and a second more sustained peak developing by about 2 h. At a higher dose the depression between the two peaks became deeper and longer with the second peak becoming more delayed and weaker. As animals got older, the doses needed to produce this sequence increased. On day 0 the increased VO2 caused by endotoxin was not accompanied by an increase in Tc. By day 3, Tc rose with the increase in VO2. We conclude that rabbits on the day of delivery respond to endotoxin with an increase in VO2 and by day 3 this is accompanied by an increase in Tc. The pattern of VO2, changes from monophasic to biphasic with increasing doses of endotoxin and the sensitivity to endotoxin decreases over the first 3 days of life.