Study on the possible entry of bacterial endotoxin and prostaglandin E2 into the central nervous system from the blood

A study has been made of the possible entry of 51Cr-bacterial endotoxin and [5,6,8,11,12,14,15(n)-3H]-prostaglandin E2 ([3H]-PGE2) into the CNS of the anesthetized cat. No radioactivity was detected in perfusates of the preoptic anterior hypothalamus or in the cerebrospinal fluid (c.s.f.) in vivo, or in brain tissue postmortem following intracarotid infusion of 51Cr-bacterial endotoxin. Intracarotid administration of [3H]-PGE2 resulted in the entry of radioactivity into the CNS of endotoxin pretreated cats. Chromatographic analysis indicated the radioactivity in c.s.f. to be associated with PGE2 and a metabolite similar to 13,14-dihydro-15-keto PGE2. Intracarotid administration of 13,14-dihydro-15-keto [5,6,8,11,12,14(n)-3H]-PGE2 resulted in the presence of the compound in the CNS of the anesthetized cat after pretreatment with bacterial endotoxin. It is concluded that PGE2 and possibly 13,14-dihydro-15-keto PGE2 but not bacterial endotoxin may enter the CNS from the cerebral circulation to elicit the febrile response to bacterial endotoxin in cats.