Regulated temperature drop may help chickens cope with infection

The discovery paves the way to a deeper understanding of the thermal responses to inflammation and infection in vertebrates. The capacity to regulate hypothermia may have been conserved from a distant ancestor or acquired independently by mammals and birds.

By André Julião  |  Agência FAPESP – A mechanism that enables rats and mice to tolerate inflammation and severe infection has been described for the first time in chickens. The study was supported by FAPESP and conducted in Brazil by researchers affiliated with São Paulo State University (UNESP) and the University of São Paulo (USP). An article reporting the results is published in the Journal of Physiology.

According to the authors, in birds, as in mammals, fever is not the only temperature change occurring in the body in response to viral and bacterial infection, and regulated hypothermia can be preferred by the organism to save energy when it needs to combat severe infection.

“We’ve known for a long time that fever is a key mechanism used by the organism to combat attackers, but heating up the body requires a good deal of energy and can be costly to the system. More recent research, some of it involving patients in intensive care, shows that the body often cools down during a severe infection as a way of saving energy to deal with the crisis,” said Kênia Cardoso Bícego, a professor at UNESP’s Faculty of Agrarian and Veterinary Sciences (FCAV) in Jaboticabal, and principal investigator for the study.

The study was part of a project led by Bícego and supported by FAPESP, and also part of the PhD research of Lara do Amaral Silva completed at FCAV-UNESP.

Until research involving mammals showed the contrary, the prevailing view of hypothermia during severe infection was that it resulted from lack of oxygen (hypoxia), inferred from the falling metabolic rate observed in experiments, which in turn was believed to be due to a collapse of the system.

“Our research shows that actually the fall in temperature reduces energy expenditure and the body, therefore, needs less oxygen,” Bícego explained. “In addition to conserving energy, it mitigates damage to lungs, liver, and other tissues. It’s a beneficial response produced by the organism itself.”

One of the co-authors of the article, Alexandre Steiner, a professor at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP), has studied the same phenomenon in rats and humans for several years now, but this is the first time regulated hypothermia has been demonstrated in birds.

Possible applications

With the data for mammals as a guide, the multidisciplinary group at UNESP conducted experiments on chicks injected with a toxic substance to simulate severe infection. The toxin was a lipopolysaccharide (endotoxin) contained in the cell walls of certain bacteria. Like rats in other studies, the chicks also exhibited a significant fall in temperature and metabolic rate.

“In a cold environment, it’s normal for skin vasoconstriction [narrowing of blood vessels] to occur in order to conserve body heat, but the infected chicks displayed vasodilation [widening of blood vessels] as their temperature fell, demonstrating activation of heat loss pathways to facilitate hypothermia,” Bícego said.

The researchers also needed a physiological demonstration that the hypothermia was controlled. In this case, they used a drug that increased metabolic rate. The hypothesis was that hypothermia was due to lack of oxygen in the body’s tissues. If this was so, the drug would have no effect on the infected chicks, but metabolic rate did increase although they remained cold. 

“We ruled out the rise in metabolic rate as a cause of hypothermia. If the organism’s response remained the same even when it was ‘tricked’ in this manner, the evidence was very strong that we were dealing with a regulated fall in temperature,” Bícego said.

In collaboration with Marcos Tulio de Oliveira, a professor at FCAV-UNESP supported by FAPESP, the group also showed that the activity of muscle mitochondria (cellular powerhouses) remained intact during hypothermia, ruling out a collapse in the energy production system as a cause of the fall in temperature.

The result does not have immediate applications but fortifies the body of evidence pointing to the importance of regulated hypothermia in veterinary medicine and treatment of severe infections, such as sepsis, in humans. “It’s a paradigm shift in our understanding of thermal responses to inflammation,” Bícego said.

In addition, the study suggests this capacity may have been inherited from a distant common ancestor of mammals and birds. Another possibility is that it was acquired independently by each group. In any event, conservation of this mechanism shows that it afforded vertebrates an advantage during their evolution.

“In broiler farming, for example, the chickens only live for 40 days and this knowledge may not be easily applied, but a possible veterinary application in poultry breeding or for other production animals and pets would be to keep cold animals at that temperature instead of trying to warm them up. Of course, this would require tests for specific clinical conditions,” Bícego said. She is currently engaged in further research to understand in more depth the mechanisms that lead to regulated hypothermia in birds.

The article “Regulated hypothermia in response to endotoxin in birds” by Lara do Amaral-Silva, Luciane H. Gargaglioni, Alexandre A. Steiner, Marcos T. Oliveira and Kênia Cardoso Bícego is at: physoc.onlinelibrary.wiley.com/doi/10.1113/JP281385.