RESPONSE OF NEWBORN AND ADULT SHEEP TO PYROGENS - RELATION BETWEEN FEVER AND BRAIN EICOSANOID CHANGES

We investigated whether the weak febrile response to pyrogens in newborns is due to a diminished activation of the putative pyrogen mediator, prostaglandin (PG)E(2). Indwelling cannulas in the third ventricle of lambs (age, 5-31 days) and adult ewes were used to collect cerebrospinal fluid (CSF) for radioimmunoassay of PGE(2). Intravenous (i.v.) endotoxin caused a smaller increase in body temperature but a larger increase in CSF PGE(2) in lambs compared to adults. PGE(2) by intracarotid infusion raised body temperature in 5 of 7 trials in 3 lambs and in 4 of 4 trials in 1 adult. Endotoxin given intracerebroventricularly (i.c.v.) induced a rise in temperature and CSF PGE(2) in the lamb but, in the adult, these responses were delayed and smaller. Interleukin-l i.c.v. and PGE(2) i.c.v. were weak pyretic agents at both ages. We conclude that the lamb's diminished febrile response to endotoxin i.v. is not caused by a lesser rise in CSF PGE(2); rather it may be due, at least in part, to reduced responsiveness to this putative mediator. Regardless of age, the sheep differs from other species in that pyrogen/PGE(2) coupling occurs primarily at a site in brain that is better accessible from blood than CSF.