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Effect of nucleus tractus solitarius lesions on fever produced by interleukin-1beta.

Abstract
Partial elimination of vagal sensory afferents by subdiaphragmatic vagal section has variously been reported to eliminate, to reduce, or to have no effect on fever produced by peripheral lipopolysaccharide and interleukin-1beta (IL-1beta). However, to adequately test the idea that vagal afferents convey immune information to the brain, all vagal input to the central nervous system must be eliminated. This was accomplished by bilateral electrolytic lesions of the nucleus tractus solitarius (NTS). Reflex bradycardia evoked by intravenous phenylbiguanide was eliminated in NTS-lesioned rats, verifying the lesion's effectiveness. IL-1beta (2 microg/kg) was given to conscious, unrestrained rats via an indwelling intraperitoneal catheter and produced rapid fever (approximately 1 degree C) with an onset latency of 15 min and peak response at 30 min, with a second, smaller peak at 130 min. NTS lesions attenuated the first fever peak, with a lesser, non-significant effect on the second peak. The thermogenic capacity of NTS-lesioned rats was evaluated using 3 different strategies: (1) thermogenesis evoked by CNS injections of prostaglandin E2, (2) 3 h exposure to a 4 degrees C environment, and (3) heat production of intrascapular brown fat produced by intravenous infusion of the beta3-adrenergic agonist BRL 37344. NTS-lesioned rats were equivalent, or even superior to control animals in their thermogenic response to these non-immune-related stimuli. Therefore, the impaired febrile response of NTS-lesioned rats to IL-1beta cannot be attributed to reduced thermogenic capacity. Finally, these results suggest that fever elicited by intraperitoneal IL-1beta is, at least in part, dependent on the integrity of NTS neurons, but also that mechanisms independent of vagal afferent projections to the NTS must also play a role in immune-to-brain signaling.
AuthorsF J Gordon
JournalAutonomic neuroscience : basic & clinical (Auton Neurosci) Vol. 85 Issue 1-3 Pg. 102-10 (Dec 20 2000) ISSN: 1566-0702 [Print] Netherlands
PMID11189016 (Publication Type: Journal Article)
Chemical References
  • Adrenergic beta-Agonists
  • Biguanides
  • Ethanolamines
  • Hypoglycemic Agents
  • Interleukin-1
  • BRL 37344
  • Dinoprostone
  • phenyl biguanide
Topics
  • Adipose Tissue, Brown (physiopathology)
  • Adrenergic beta-Agonists (pharmacology)
  • Animals
  • Biguanides (pharmacology)
  • Bradycardia (chemically induced)
  • Cold Temperature
  • Denervation
  • Dinoprostone (pharmacology)
  • Ethanolamines (pharmacology)
  • Fever (chemically induced, immunology, pathology)
  • Hypoglycemic Agents (pharmacology)
  • Injections, Intraperitoneal
  • Interleukin-1 (pharmacology)
  • Male
  • Neuroimmunomodulation (drug effects, physiology)
  • Neurons, Afferent (immunology)
  • Rats
  • Rats, Long-Evans
  • Solitary Nucleus (immunology, pathology)
  • Thermogenesis (immunology)
  • Vagus Nerve (cytology, immunology)

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