Comparison of endotoxin and leukocytic pyrogen pyrogenicity in newborn guinea pigs

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Abstract
Guinea pigs < 8 days old generally are unable to develop fever (.DELTA.Tre [rectal temperature change] > 0.5.degree. C) in response to a standardized dose of endotoxin (2 .mu.g/kg i.v. of Salmonella enteritidis [SE]). This study determined whether this lack of responsiveness might be due to an incapacity of leukocytes from young neonates to produce sufficient leukocytic pyrogen (LP). Three series of experiments were performed at Ta = 27.degree. C: guinea pigs aged 0-2, 4 and 8 days were injected i.v. with 2, 4, 8 or 16 .mu.g/kg of SE, 0.1, 0.5 or 1.0 ml of LP generated by 8 .mu.g of SE/25 .times. 106 leukocytes from adult guinea pigs (LPa) or 0.1 or 1.0 ml of LP generated by 8 .mu.g of SE/25 .times. 106 leukocytes from 0-5, 6-12 and 13-16 day old guinea pigs (LPn). Adult guinea pigs received i.v. 1.0 ml of LPa or LPn. Fever could be induced in these animals from birth, but the required doses of SE, LPa and LPn were greater the younger the guinea pigs. Under these conditions LPn, regardless of the donors'' ages, produced fever in all the recipients. The pyrogenic unresponsiveness of newborn guinea pigs to endotoxin may be related not to an inability of leukocytes from these neonates to elaborate LP, but rather to an insensitivity of their hypothalamic febrogenic mechanisms to low levels of LP.