Prostaglandin E2 Enters the Brain following Stimulation of the Acute Phase Immune Response a

Fever is a major manifestation of the acute phase of the immune response to infection by a variety of microorganisms including bacteria and viruses. The rise iv body temperature which characterises a febrile episode is thought to be the result of the actions of prostaglandin E, (PGE,) in the preoptic anterior hypothalamic region of the brain. The actions of exogenous pyrogenic agents such as bacterial endotoxin (lipopolysaccharide) and polyinosinic : polycytidylic acid (poly I : C) are thought to be mediated by the endogenous production of interleukin-1 (IL1) which concomitantly stimulates the biosynthesis of PGE,. Both the exogenous pyrogens and IL-1 have been shown to stimulate the biosynthesis of PGE, both in vitro and in vivo but are unable to cross the blood brain barrier and penetrate into the brain. It has been shown that radiolabelled lipopolysaccharide given peripherally is not detected in cerebrospinal fluid (CSF) collected from the cisterna magna whilst being able to produce fever indicating that the lipopolysaccharide does not cross the blood brain barrier.3 Similarly it has also been shown that IL-1 does not cross the blood brain barrier. Purified natural ['251]IL-1 and recombinant ['251]IL-la have been administered peripherally, and it has been demonstrated that no radioactivity enters the brain paren~hyma.~.' In addition no interleukin-1 can be detected in the CSF of cats after the i.v. administration of endotoxin.6 Measurements of IL-1 activity in the study of Coceani et a1.6 were carried out on samples of CSF taken during the rising phase of the endotoxin fever and at the peak of the febrile response indicating that the increase in body temperature did not occur