The Immune System Feels the Heat

A major unsolved mystery in immunity relates to the mechanisms underlying the protective action of fever. A review of the current understanding of how fever impacts the immune system is offered by researchers from Roswell Park Comprehensive Cancer Center and published in the recent journal of Nature Reviews Immunology.

“Fever considered a ‘first responder’ to infection has been conserved in warm-blooded and cold-blooded animals and organisms for more than 600 million years of evolution,” says Sharon Evans, PhD, Professor of Oncology, Department of Immunology at Roswell Park. “Understanding the complicated interactions involved in a simple fever response will provide valuable insights into how we may harness those mechanisms may help fight cancer.” 

Key points of the review article are:

• The hallmark fever response during infection and disease has been maintained through hundreds of millions of years in endothermic (warm-blooded) and ectothermic (cold-blooded) species.
• Fever increases the probability of an effective natural and adaptive immune response.
• A fever-associated cell signaling molecule (IL-6) plays a role in thermoregulation and influences events that result in an effective immune response.
• There is emerging evidence that intersections between the nervous system and thermogenesis can significantly influence immune cell function.
• The thermal element of fever serves as a systemic alert system that broadly promotes immune surveillance in a setting of infection and disease.

“The cause-and-effect relationship between body temperature and outcome to infectious challenges has been shown to have a profound effect on the probability of survival. The mechanistic insights into the immune-protective nature of fever have opened up new avenues to exploit the immunostimulatory activities of thermal stress in the context of cancer therapy,” adds Dr. Evans.

New insights regarding the benefit of the heat component of a natural fever response are being exploited by the research programs of Dr. Evans and Elizabeth Repasky, PhD, to boost the efficacy of cancer immunotherapy.