Leukocytic pyrogen effects on prostaglandins in hypothalamic tissue slices.
Some studies suggest that leukocytic pyrogen (LP) increase hypothalamic prostaglandins which, in turn, affect hypothalamic thermoregulatory neurons to produce fever. The present study used radioimmunoassays to quantitate the ability of guinea pig hypothalamic tissue slices to produce prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2). Dose- and time-dependent prostaglandin increases occurred when these slices were perfused with LP media. Steady-state levels of tissue release were reached at 0-3 min for 6-keto-PGF1 alpha, at 6-9 min for PGE2 and PGF2 alpha, and at 12-15 min for TxB2. With the exception of 6-keto-PGF1 alpha, all substances showed continuous dose-response relationships for concentrations ranging from 0.001 to 0.25 LP dilutions. Tissue PGE2, for example, was 0.7 pg X min-1 X mg-1 with the 0.001 LP dilution and 8.7 pg X min-1 X mg-1 with the 0.25 LP dilution. Indomethacin blocked much of the LP-induced prostaglandin increase. Although there is a relationship between hypothalamic LP and prostaglandins in response to physiological LP levels, tissue prostaglandins are several orders of magnitude lower than concentrations necessary to produce fever by hypothalamic microinjection. This suggests that prostanoids, such as PGE2, may not be the sole mediators of fever induced by leukocytic pyrogen.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*
D007375:Interleukin-1; D011453:Prostaglandins; C008270:leukocyte endogenous mediator; D007213:Indomethacin