Amro Soliman

Canada

Fever: An Evolutionarily Conserved Regulator of Immune Defense

Amro M. Soliman1, Farah Haddad2, Daniel Barreda2

1. Department of Biological Sciences, Concordia University of Edmonton, Edmonton, Canada
2. Department of Biological Sciences, University of Alberta, Edmonton, Canada

Abstract

Background

Fever is an evolutionarily conserved response to infection observed across endothermic and ectothermic vertebrate species. Despite its ubiquity, the adaptive significance of fever and its mechanistic role in enhancing immune functions remain incompletely understood. In ectothermic animals, fever manifest behaviourally, a voluntary migration to warmer environments to increase host’s body temperature (i.e., behavioural fever). This model offered a powerful model for examining how fever modulates immune responses and influences host–pathogen dynamics.

Methods

A teleost fish model was used to study the impact of fever on immune activation during infection. Fish were experimentally infected with Aeromonas veronii and housed in a custom-built swim chamber that allowed voluntary thermal selection. Immune parameters, including leukocyte recruitment, phagocytic activity, cytokine expression and bacterial clearance, were assessed in febrile versus afebrile fish. Parallel experiments involving mechanically induced hyperthermia were conducted to distinguish natural thermoregulatory effects from artificial heat exposure.

Results

Infected fish consistently selected warmer temperatures, demonstrating a robust behavioural fever response. Febrile fish exhibited enhanced leukocyte recruitment to infection sites, increased phagocytic activity, and upregulated expression of key pro-inflammatory cytokines. These immune enhancements were associated with faster bacterial clearance, even though the pathogen displayed optimal growth at elevated temperatures. This was further associated with enhanced restoration of tissue homeostasis. Mechanically induced hyperthermia failed to replicate these benefits, indicating that behavioural fever is an integrated adaptive process rather than a simple thermal effect.

Conclusions

This work demonstrates that fever represents an evolutionarily conserved and actively regulated immune strategy that optimizes host defense against infection. By coupling thermoregulatory behavior with enhanced immune function, behavioral fever exemplifies the deep evolutionary link between physiology and immunity in vertebrates. Ongoing research aims to identify the molecular and signaling pathways underlying this adaptive response, with particular focus on the potential fever-induced metabolic programming in immune cells.