Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid

1. In the unanaesthetized cat, rectal temperature was recorded and c.s.f. was collected from a Collison cannula implanted into the third ventricle with its opening lying in close proximity to the anterior hypothalamus. Samples of c.s.f. were collected from the same cat, during normal temperature, during fever produced by Shigella dysenteriae injected into the third ventricle and during the fall in temperature which occurred when the antipyretic paracetamol was injected intraperitoneally during the pyrogen fever.2. The samples of c.s.f., when tested on the rat stomach fundus preparation, caused contractions which were not due, or at most to a small degree only, to 5-hydroxytryptamine, as they were resistant to BOL. They were therefore probably due to a prostaglandin-like substance.3. When assayed against PGE(1), the activity of c.s.f. collected from cats when their body temperature was normal corresponded to between 1.3 and 10 ng/ml. The values, whether low or high, rose over 2.5-4 times to between 4 and 35 ng/ml. in c.s.f. collected during pyrogen fever; they were again low, between 1.5 and 6 ng/ml., in samples collected when the fever had been brought down by paracetamol, but rose again with the return of fever.4. The results provide direct evidence for the theory that fever produced by pyrogens results from their ability to increase synthesis and release of prostaglandins, and that antipyretics bring down the fever because they inhibit the increased synthesis.