Endogenous pyrogen release by fetal sheep and pregnant sheep blood leukocytes

Abstract

These experiments were undertaken to determine if fetal blood leukocytes are capable of producing endogenous pyrogen (EP), as neither the fetal nor newborn lamb can produce a fever in response to bacterial endotoxin. Maternal leukocytes were also tested for their ability to produce EP as the near-term pregnant sheep cannot produce a fever in response to bacterial endotoxins or EP. The results demonstrate that both fetal and near-term maternal leukocytes can produce EP, thus supporting experimental evidence that the inability of the newborn and near-term mother to become febrile is due to a process other than lack of EP production.

The role of tumour necrosis factor-alpha (TNF-α) in fever and the acute phase reaction in rabbits

“…There are already a number of differences in the nature of Gram-negative and Gram-positive fever responses, including the development of tolerance [9,27] and responses in new-born [10] and pregnant [13] animals. We can now add to this list that the role of TNF-α apparently differs in the two fever responses.…”

Fever's Glass Ceiling

“…The search for endogenous antipyretics responsible for limiting the height of the febrile response began in earnest with studies of the temporarily blunted febrile response of periparturient ewes and newborn lambs to challenges with iv endotoxin [90]. Unable to identify a thermoregulatory defect or an inability of such animals to synthesize and release endogenous pyrogens, Kasting et al [91] hypothesized the existence of an endogenous antipyretic agent responsible for the state of pyrogen unresponsiveness. AVP emerged as a likely candidate for such an endogenous antipyretic, after several groups of investigators [92][93][94] showed that the low-molecular-weight neuropeptide was present in increased concentrations in the circulation of pregnant ewes at the time oftheir diminished responsiveness to challenge with fever-inducing agents.…”