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 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 (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.