European Journal of Applied Physiology

, 103:561

Interleukin-1 receptor antagonist restores homeostatic function and limits multiorgan damage in heatstroke


  • Kun-Hung Shen
    • Department of UrologyTaipei Medical University
    • Department of UrologyChi Mei Medical Center
  • Chen-Kuei Chang
    • Department of SurgeryMackay Memorial Hospital
    • Graduate Institute of Injury Prevention and ControlTaipei Medical University and Wan-Fan Hospital
    • Department of BiotechnologySouthern Taiwan University of Technology
    • Department of Medical ResearchChi Mei Medical Center
  • Ching-Ping Chang
    • Department of BiotechnologySouthern Taiwan University of Technology
    • Department of Medical ResearchChi Mei Medical Center
Original Article

DOI: 10.1007/s00421-008-0755-1

Cite this article as:
Shen, K., Chang, C., Lin, M. et al. Eur J Appl Physiol (2008) 103: 561. doi:10.1007/s00421-008-0755-1


We attempt to investigate whether interleukin-1 receptor antagonist (IL-1ra) therapy improves survival during heatstroke by attenuating multiorgan dysfunction. Anesthetized rabbits, immediately after the onset of heatstroke, are divided into three major groups and given: nothing, normal saline (1 ml/kg, i.v.), or IL-1ra (200–400 μg per 1 ml/kg, i.v.). They are exposed to ambient temperature of 40°C to induce heatstroke. Another group of rabbits is exposed to room temperature (24°C) and used as normothermic controls. Hyperthermia, hypotension, cerebral ischemia and edema, hepatic and renal failure, increased levels of both nitric oxide metabolites (NOx) and dihydroxybenzoic acid (DHBA) in plasma, hyperkalemia, respiratory alkalosis, and metabolic acidosis and hypoxia are all observed in vehicle-treated heatstroke animals. When the vehicle-treated animals undergo heat stress, their survival time values are found to be 12–18 min. Resuscitation with IL-1ra dose-dependently improves survival time (duration, 132–303 min). As compared with vehicle-treated heatstroke rabbits, IL-1ra therapy significantly causes attenuation of heatstroke-induced hyperthermia, hypotension, cerebral ischemia and edema, intracranial hypertension, hepatic and renal dysfunction, NOx and DHBA overproduction, hyperkalemia, hypoxia, respiratory alkalosis, and metabolic acidosis. The results indicate that IL-1ra therapy may restore tissue blood flow and homeostatic function, and limit multiorgan dysfunction and death in heatstroke.


HeatstrokeInterleukin-1 receptor antagonistMultiorgan dysfunctionHyperkalemiaAcidosis

Copyright information

© Springer-Verlag 2008