Fever, the evidence base



Human monocyte stimulation by experimental whole-body hyperthermia.

The thermal effect of fever has been associated with better survival and a shorter duration of disease in cases of infection.

Twelve healthy volunteers were immersed in a 39.5 degrees C hot water

The expression of immunologically active components of monocytes increased

Downregulation of aspects of inflammation

Comparable changes in monocyte receptor expression were observed after in vitro hyperthermia.

We conclude that the thermal effect of fever directly activates monocytes, which increases their ability to respond to bacterial challenge.

Effect of a Single Finnish Sauna Session on White Blood Cell Profile and Cortisol Levels in Athletes and Non-Athletes Journal of Human Kinetics 2013
15-minute sauna sessions until their core temperature rose by 1.2°C
After the sauna session, an increased number of white blood cells, lymphocyte, NK cells, neutrophil and basophil counts was reported in the white blood cell profile.

Immune changes in humans during cold exposure:
effects of prior heating and exercise Journals of Physiology 2020

Hot-water bath (39.5– 40°C) for at least 2 h to raise core temperature (2.0–
2.5°C); significant increases total and differential leukocyte counts.

Fever and the thermal regulation of immunity: the immune system feels the heat (National review of immunology 2015)
Antipyretic drugs to diminish fever correlates with a 5% increase in mortality in human populations infected with influenza virus
Mounting evidence that the 1 – 4°C in core body temperature that occurs during fever is associated with improved survival and resolution of many infections.
Cold blooded animals
Fever activates NK cells, monocytes and lymphocytes
Heat reduces transcription of pro-inflammatory cytokines in macrophages

Thermoregulation as a disease tolerance defence strategy Pathogens and Disease, 74, 2016
Average percent increase in metabolism for every 1◦C of fever is ∼13%
Heat shock factor 1 (produced in fever) inhibits monocyte production of pro-inflammatory cytokines
Behavioural modifications; anorexia, sleep changes, social withdrawal – known as sickness-induced behaviours

Clinical course and risk factors for mortality of adult
inpatients with COVID-19 in Wuhan, China: a retrospective
cohort study

Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.

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