Interleukin-1 receptor antagonist restores homeostatic function and limits multiorgan damage in heatstroke.
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 microg per 1 ml/kg, i.v.). They are exposed to ambient temperature of 40 degrees C to induce heatstroke. Another group of rabbits is exposed to room temperature (24 degrees C) and used as normothermic controls. Hyperthermia, hypotension, cerebral ischemia and edema, hepatic and renal failure, increased levels of both nitric oxide metabolites (NO ( x ) (-) ) 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, NO ( x ) (-) 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.
Shen
Kun-Hung
KH
Department of Urology, Taipei Medical University, Taipei, Taiwan.
Chang
Chen-Kuei
CK
Lin
Mao-Tsun
MT
Chang
Ching-Ping
CP
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001806:Blood Urea Nitrogen; D001831:Body Temperature / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism; D018883:Heat Stroke / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006706:Homeostasis / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007427:Intracranial Pressure / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
D004573:Electrolytes; D053590:Interleukin 1 Receptor Antagonist Protein; D017382:Reactive Oxygen Species