Effect of propranolol on endotoxin-induced pyrogenesis in newborn and adult guinea pigs

Abstract

Nonshivering thermogenesis (NST) is the prevailing mechanism of fever production in newborn (the first 2-3 wk of life) and adult cold-acclimated guinea pigs. This study determined whether this process is mediated by noradrenergic sympathetics. The temperatures in the interscapular brown fat pad (Tbat) and the colon (Tre), the rate of O2 consumption (.ovrhdot.VO2), and shivering activity were measured continuously for 5 h at 27.degree. C ambient temperature in 8- and 16-day-old and adult cold-acclimated guinea pigs following 2 .mu.g/kg i.v. of Salmonella enteritidis endotoxin, with and without 6.0 mg/kg of propranolol (a .beta.-adrenergic blocker) injected i.p. 2 min before the endotoxin. In the older animals, the increase in Tbat normally produced by endotoxin was reduced by propranolol administration, but shivering set in, maintaining both .ovrhdot.VO2 and Tre at their febrile levels. In the newborn animals, Tbat also was decreased by propranolol, but shivering did not set in; .ovrhdot.VO2 and Tre fell below their feblow their febrile values. Endotoxin-induced NST is probably controlled by noradrenergic sympathetics. The failure of NST to be replaced in these newborn guinea pigs by visible shivering might be related to other observations that the onset of shivering at this age occurs only when Tre is significantly reduced.