Reduced Febrile Responses to Peripheral and Central Administration of Pyrogen in Aged Squirrel Monkeys

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10–14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE₂ in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.