Evans · Nature reviews. Immunology 2015 · narrative review · n=?

Fever and the thermal regulation of immunity: the immune system feels the heat.

Cited 1296 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic and physiological literature without systematic search methodology or new clinical data.

PubMed 25976513 · doi:10.1038/nri3843 · record verified 2026-08-26

What was done

This narrative review synthesizes literature on the evolutionary conservation and neuro-physiological mechanisms of the fever response. The authors review evidence regarding how thermal elements of fever regulate innate and adaptive immunity, the multi-faceted roles of interleukin-6 (IL-6) in fever induction and lymphocyte trafficking to lymphoid organs, and the influence of adrenergic thermogenic signaling on immune cell function.

What was found

The abstract reports no quantitative metrics or effect sizes. It qualitatively describes fever as an evolutionarily conserved mechanism across vertebrates (spanning >600 million years) that confers survival benefit in infection, driven by integrated physiological and neuronal circuits that activate immune responses, mobilize lymphocytes via IL-6, and alter immune function through adrenergic pathways.

Why it matters

It outlines how elevated body temperature directly coordinates immune defense rather than acting merely as a passive bystander symptom of infection.

Limits

As a narrative review, it lacks a systematic search strategy, risk of bias assessment, or quantitative synthesis. The abstract provides no empirical clinical data, sample sizes, or outcome measurements.

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