Glutathione deficiency attenuates endotoxic fever in rats.

OBJECTIVE

Glutathione constitutes the first line of the cellular defence mechanism against oxidative stress, and according to published data it is required by a number of factors that are involved in fever mechanism. The aim of the present study was to investigate whether or not glutathione deficiency can modulate a course of the fever induced by endotoxin (LPS).

METHODS

Intraperitoneal injection of LPS from Escherichia coli was used to provoke fever in Wistar rats. The level of liver glutathione was decreased by administration of phorone (Pho). Deep body temperature (Tb) in free running rats was recorded using a biotelemetry system. The concentration of TNF-α was estimated. Next, the supplementation of TNF-α was done using recombinant rat TNF-α.

RESULTS

Animals with decreased glutathione level responded with diminished fever after LPS injection (average Tb in Pho/LPS-treated and oil/LPS-treated animals were 36.90° ± 0.10 °C and 37.80° ± 0.15 °C, respectively). This response was accompanied by a significant attenuation of LPS-induced increase in TNF-α concentration (in the Pho/LPS-treated group it was 10.68 pg/mL ± 2.24, vs. 113.35 pg/mL ± 13.93 in oil/LPS-treated rats). Supplementation with TNF-α partially restored fever.

CONCLUSIONS

Based on these data, we conclude that glutathione deficiency modifies the LPS-induced fever, in a TNF-α related manner.