Regulated hypothermia in response to endotoxin in birds

Abstract

Key points: The costs associated with immune and thermal responses may exceed the benefits to the host during severe inflammation. In this case, regulated hypothermia instead of fever can occur in rodents as a beneficial strategy to conserve energy for vital functions with consequent tissue protection and hypoxia prevention. We tested the hypothesis that this phenomenon is not exclusive to mammals, but extends to the other endothermic group, birds. A decrease in metabolic rate without any failure in mitochondrial respiration, nor oxygen delivery, is the main evidence supporting the regulated nature of endotoxin-induced hypothermia in chicks. Thermolytic mechanisms such as tachypnea and cutaneous vasodilatation can also be recruited to facilitate body temperature decrease under lipopolysaccharide treatment, especially in the cold. Our findings bring a new perspective for evolutionary medicine studies on energy trade-off in host defence because regulated hypothermia may be a phenomenon spread among vertebrates facing a severe immune challenge.

Abstract: A switch from fever to regulated hypothermia can occur in mammals under circumstances of reduced physiological fitness (e.g. sepsis) to direct energy to defend vital systems. Birds in which the cost to resist a pathogen is additive to the highest metabolic rate and body temperature (T_b ) among vertebrates may also benefit from regulated hypothermia during systemic inflammation. Here, we show that the decrease in T_b observed during an immune challenge in birds is a regulated hypothermia, and not a result of metabolic failure. We investigated O₂ consumption (thermogenesis index), ventilation (respiratory heat loss), skin temperature (sensible heat loss) and muscle mitochondrial respiration (thermogenic tissue) during T_b fall in chicken chicks challenged with endotoxin [lipopolysaccharide (LPS)]. Chicks injected with LPS were also tested regarding the capacity to raise O₂ consumption to meet an increased demand driven by 2,4-dinitrophenol. LPS decreased T_b and the metabolic rate of chicks without affecting muscle uncoupled, coupled and non-coupled mitochondrial respiration. LPS-challenged chicks were indeed capable of increasing metabolic rate in response to 2,4-dinitrophenol, indicating no O₂ delivery limitation. Additionally, chicks did not attempt to prevent T_b from falling during hypothermia but, instead, activated cutaneous and respiratory thermolytic mechanisms, providing an additional cooling force. These data provide the first evidence of the regulated nature of the hypothermic response to endotoxin in birds. Therefore, it changes the current understanding of bird's thermoregulation during severe inflammation, indicating that regulated hypothermia is either a convergent trait for endotherms or a conserved response among vertebrates, which adds a new perspective for evolutionary medicine research.

Keywords: anapyrexia; birds; hypothermia; inflammation; metabolic rate; peripheral vasodilatation; tachypnea.