Connection of fever and immunological reactions (for specialists)

The elevation of body temperature is closely tied to a number of immunological reactions.

For approx. 600 million years only in vertebrates has evolution been “polishing” in this direction to develop a complexly regulated system, in which the entire body is involved (149). This was preceded by an even longer evolutionary process. See our separate article „The meaning and evolution of fever” on this.

Fever synchronously exerts its immunological action through several mechanisms:

1) by thermal effects (9)

2) humorously (10) and

3) through several cellular (11) mechanisms:

  • by activation (148), proliferation and maturation of leukocytes,
  • by stimulating neutrophil and monocyte motility (a4 integrins, 148), migration, phagocytosis, -pinocytosis,
  • T cells - faster activation and faster growth (higher cytotoxic activity),
  • accelerated antibody production,
  • accelerated the processing and presentation of antigens by dendritic cells,
  • presentation on T cells as well as migration to lymph nodes (FAK-RhoA, 148).

NF-kB and A20 proteins that activate the cell clock of immune cells are more active at higher temperatures.

The activity of heat shock proteins (such as Heat Shock Protein 90) and a4 integrins is closely related to T cell activity (148).

It is probably through this mechanism, that fever increases the anti-bacterial effect of antibiotics (7-10). Thus, when antiviral and antibacterial drugs are used when indicated, they tend to be more effective if the patient also has an optimum fever.

Unindicated inhibition of fever, or inhibition for convenience alone, also suppress these immune mechanisms.

The administration of antibiotics to a patient in good general condition is not indicated for three days (124).


Fever-causing pyrogens:

1) Exogenous pyrogens (these activate the production of endogenous pyrogens during infections)

  • Gram negative endotoxins
  • G positive toxins
  • other infectious agents

2) Endogenous pyrogens

  • cytokines: IL-1α, IL-1β, IL-6, IL-11, TNF-α, IFN-α, -β and γ, oncostatin M, LIF, prostaglandins
  • they are produced by a wide variety of cells, most notably monocytes and macrophages, mesangial cells, keratinocytes and other epithelial cells at the site of infection
  • these triggered a set-point rise when reaching the hypothalamus

Multiple serum reactant changes can be detected during infection (135):

Positive acute phase reactants: procalcitonin (PCT), C-reactive protein, complements, cytokines, coagulation proteins, alpha-1-antitrypsin, alpha-1-chymotrypsin, haptoglobin, haemopexin, ceruloplasmin, ferritin, cytokines.

Negative acute phase reactants: albumin, transferrin, serum iron, fibronectin.

A common mistake in this case is oral substitution of iron. We do not recommend routine administration for a period of two weeks after a simple infection, unless justified later, based on a detailed lab results.


Refer to the literature by numbers in this document here: References

Version update 03 October 2020