Effects of Leukocytic Pyrogen (Interleukin-1) on Local Cerebral Glucose Utilization in Rats with and without Premedication with Indomethacin or Dexamethasone

Changes in body temperature were recorded in freely moving rats given phosphate-buffered saline or leukocytic pyrogen (interleukin-1) while the animals were in an infant incubator maintained at 25.5 ± 0.5°C. The leukocytic pyrogen increased body temperature by at least 1°C within 1 h. This rise in temperature was prevented by premedication with indomethacin (10 mg/kg) but not dexamethasone (0.5 mg/kg) given 15 min before the leukocytic pyrogen. Local rates of glucose utilization were measured in 47 regions of the central nervous system. In none of the regions previously reported to have an increased rate of glucose utilization associated with an ambient temperature of 32.5°C (McCulloch et al., 1982b) was an increase found in the present experiments. It was concluded that the intensity of the changes in local cerebral glucose utilization in response to the fever caused by the leukocytic pyrogen was insufficient to be measured. Neither indomethacin nor dexamethasone caused remarkable changes in rates of local glucose utilization.

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.