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Role of fever in disease
Matthew J Kluger1, Wieslaw Kozak1, Carole A Conn1
1Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA.
Abstract:
Infection, trauma, and injury result in a stereotypical response that includes loss of food appetite, increased sleepiness, muscle aches, and fever. For thousands of years fever was considered a protective response, and fevers were induced by physicians to combat certain infections. But with the advent of antipyretic drugs, physicians started to reduce fevers, and fever therapy was virtually abandoned. As a result of (1) studies on the evolution of fever, (2) further understanding of just how tightly the process of fever is regulated, and (3) detailed studies on how fever affects host morbidity and mortality, the view of fever as a host defense response has reemerged. However, data indicate that not all fevers are protective and that high fevers are maladaptive. These issues are discussed in the context of the evolution of host defense responses versus modern medical technology. In short, we speculate that patients who would not have survived severe sepsis in the past are now being kept alive and that the occasionally high fevers seen in these patients may be maladaptive.
Insights
Fever, a natural host defense, can be protective but also harmful. Modern medicine keeps patients with severe sepsis alive, but their high fevers may now be maladaptive.
Area of Science:
- Physiology
- Immunology
- Evolutionary Biology
Background:
- Fever is a stereotypical response to infection, trauma, and injury, historically used therapeutically.
- Antipyretic drugs led to the abandonment of fever therapy, shifting medical focus to fever reduction.
- Recent research on fever's evolution, regulation, and impact on host health has revived its consideration as a defense mechanism.
Purpose of the Study:
- To re-evaluate the role of fever as a host defense response in light of modern medical advancements.
- To discuss the adaptive and maladaptive aspects of fever in contemporary clinical contexts.
- To explore the interplay between evolutionary host defense mechanisms and modern medical technology.
Main Methods:
- Review of evolutionary studies on fever.
- Analysis of research on fever regulation.
- Examination of data on fever's effects on host morbidity and mortality.
Main Results:
- Fever is a tightly regulated physiological response with a complex role in host defense.
- While often protective, fever is not universally beneficial and can be maladaptive, particularly at high temperatures.
- Modern medical interventions allow survival of patients with severe sepsis who might not have previously survived.
Conclusions:
- The re-emergence of fever as a host defense concept requires nuanced understanding.
- High fevers in critically ill patients, especially those surviving severe sepsis due to modern medicine, may represent a maladaptive response.
- Balancing evolutionary host defenses with modern medical interventions is crucial for optimizing patient outcomes.