Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens.
Conscious cats were used to study the local release of prostaglandin (PG) E2 and thromboxane (Tx) B2 (the stable TxA2 by-product) from the preoptic-anterior hypothalamus (AH-POA) and the tuberal-posterior hypothalamus (PH-Tu) using a modified "push-pull" perfusion procedure. In the absence of fever, PGE2 release was steady from the 2nd h of perfusion onward, its rate at either site ranging between 0.08 and 0.12 pg/min. Local treatment with probenecid (1 mM) increased PGE2 release about threefold. Compared with PGE2, basal release of TxB2 was greater (0.15-0.43 pg/min) and, occasionally, tended to fall with time. Both compounds were found in higher amounts (2- to 10-fold increase) after locally injecting endotoxin, and the effect was greater in AH-POA than PH-Tu. Conversely, intravenous endotoxin (bolus) or interleukin 1 (IL-1) (bolus plus infusion) at doses causing a sustained fever selectively stimulated the formation of PGE2, but the response itself did not differ between AH-POA and PH-Tu. In either region, the degree of enhancement in PGE2 release correlated with the magnitude of the fever. Intravenous indomethacin (2 mg/kg) reversed both the fever and PGE2 elevation. These findings support an intermediary role for PGE2 in the central action of pyrogens and the ensuing fever. Blood-borne pyrogens may act at multiple sites in brain, which are tentatively identified with the circumventricular organs.
Sirko
S
S
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Bishai
I
I
Coceani
F
F
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D015232:Dinoprostone / Q000096:biosynthesis*; D004731:Endotoxins; D005260:Female; D005334:Fever / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011749:Pyrogens / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013929:Thromboxane B2 / Q000096:biosynthesis*
D004731:Endotoxins; D007375:Interleukin-1; D011749:Pyrogens; D011994:Recombinant Proteins; D013929:Thromboxane B2; D015232:Dinoprostone; D011339:Probenecid; D007213:Indomethacin