Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens

• Published in: The American journal of physiology Vol. 256; no. 3 Pt 2; p. R616
• Main Authors: Sirko, S, Bishai, I, Coceani, F
• Format: Journal Article
• Language: English
• Published: United States 01.03.1989
• Subjects: Animals; Body Temperature - drug effects; Cats; Dinoprostone - biosynthesis; Endotoxins; Female; Fever - metabolism; Hypothalamus - drug effects; Hypothalamus - metabolism; Indomethacin - pharmacology; Interleukin-1 - pharmacology; Male; Probenecid - pharmacology; Pyrogens - pharmacology; Recombinant Proteins - pharmacology; Reference Values; Thromboxane B2 - biosynthesis
• ISSN: 0002-9513
• DOI: 10.1152/ajpregu.1989.256.3.r616

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.