Cytokines and cytokine inducers stimulate prostaglandin E-2 entry into thebrain

Cytokine inducers and cytokines increase the circulating level of prostagla ndin E-2 (PGE(2)) during the acute-phase immune response. This occurs simul taneously with the onset of fever, indicating that brain levels of PGE, als o increase. This raises the possibility that PGE2 produced in the periphera l circulation, not necessarily at distant sites from the brain, may penetra te the brain and be present in the cerebrospinal fluid (CSF). Blood and CSF levels of PGE, in rabbits were measured by radioimmunoassay during fever s timulated in response to lipopolysaccharide (LPS), polyinosinic:polycytidyl ic acid (poly I:C) and interleukin-1 (IL-1) given i.v. The effect of the pr ostaglandin synthesis inhibitor ketoprofen on these parameters was also stu died. In addition, the level of radioactivity in the CSF was measured follo wing, the administration of [I-125]-labelled PGE(2) i.v. during fever induc ed by LPS, poly I:C, IL-1 or tumor necrosis factor alpha (TNF alpha). Both LPS and poly I:C stimulated an increase in plasma and CSF levels of PGE2 ov er a 5-h period with a peak at 60 min and 90 min, respectively, which occur red in parallel with the changes in body temperature. Ketoprofen abolished the rise in plasma and CSF PGE2 levels and the rise in body temperature in response to LPS, poly I:C and IL-1. In experiments where animals were given [I-125]-labelled PGE(2) i.v., radioactivity well above the background leve l was measured in samples of CSF collected from LPS-, poly I:C-, IL-l- or T NF alpha -pretreated animals. In contrast the radioactivity present in samp les of CSF perfusate collected from control (saline-treated) animals was in distinguishable from the background level. These data indicate that cytokin e inducers and cytokines increase the mass level of PGE, in blood and CSF a nd also increases the entry, from the peripheral circulation, of radiolabel led PGE2 into the third cerebral ventricle.