High-dose fentanyl does not suppress interleukin-1 beta-induced increases in plasma ACTH and corticosterone in rats.
BACKGROUND
High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) is one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether high-dose fentanyl may influence the IL-1 beta-induced alterations in plasma ACTH and corticosterone in rats.


METHODS
Plasma ACTH, corticosterone, blood pressure, heart rate and acid-base status were determined in either awake or fentanyl-anesthetized animals immediately before and after either phosphate buffered saline or IL-1 beta administration. Fentanyl anesthesia was induced by bolus intravenous injections of fentanyl at 50 micrograms/kg and pancuronium bromide at 0.2 mg/kg, and maintained by continuous administrations of fentanyl at 100 or 200 micrograms.kg-1.h-1 and pancuronium bromide at 0.4 microgram.kg-1.h-1.


RESULTS
In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 microgram/kg increased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 micrograms/kg did not influence plasma ACTH. A noxious stimulus with tail clamping for 30 min did not significantly alter plasma ACTH in fentanyl-anesthetized rats. Fentanyl reduced the basal plasma corticosterone, but it did not modulate the increases in plasma ACTH and corticosterone after the administration of IL-1 beta at 1 microgram/kg. Fentanyl moderately increased the basal blood pressure and heart rate, but it moderately attenuated the IL-1 beta-induced elevations of blood pressure and heart rate. IL-1 beta moderately decreased PCO2 in awake animals.


CONCLUSIONS
Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 beta-mediated activation of the pituitary-adrenal axis in rats.
Numai
T
T
Department of Anesthesiology, Chiba University School of Medicine, Japan.
Inaba
H
H
Mizuguchi
T
T
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D007375:Interleukin-1; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D005283:Fentanyl; D003345:Corticosterone