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

1 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 ([3H5-PGE2) into the CNS of the anaesthetized cat. 2 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 post mortem following intracarotid infusion of 51Cr-bacterial endotoxin. 3 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. 4 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 anaesthetized cat after pretreatment with bacterial endotoxin. 5 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.