To protect or to kill: A persisting Darwinian immune dilemma

•Phylogenetically old cytokines can induce damage and neuroendocrine and metabolic derangements.•These effects can mediate negative selection of infected less adapted individuals.•Immune-mediated negative selection can favor emergence and expansion of species.•Anti-homeostatic immune programs are pr...

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Bibliographic Details
Published in:Brain, behavior, and immunity behavior, and immunity, 2022-07, Vol.103, p.205-214
Main Authors: Besedovsky, Hugo O., Del Rey, Adriana
Format: Article
Language:English
Subjects:
Acute and chronic diseases
Anti-homeostatic immune effects
Biomarkers
Chronic Disease
Cytokines
Evolution
Homeostasis
Humans
Individual and species consequences
Infectious diseases
Physiological control mechanisms
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Summary:•Phylogenetically old cytokines can induce damage and neuroendocrine and metabolic derangements.•These effects can mediate negative selection of infected less adapted individuals.•Immune-mediated negative selection can favor emergence and expansion of species.•Anti-homeostatic immune programs are preserved because evolution is a permanent process.•Harmful immune programs can be expressed during acute and chronic pathologies. The immune system, which evolved as a protective system, can paradoxically mediate lethal effects when it is over-activated. These effects can be traced back to infected insects and are mainly mediated by phylogenetically old cytokines that have been found already in starfishes and sponges. We hypothesize that these anti-homeostatic effects are important for restricting the cumulative risk of transmission of highly mutating environmental pathogens that may endanger species, particularly when they start to originate and expand. Considering the Darwinian view that evolution is a permanent process, this anti-homeostatic program is preserved and expressed even when there is no risk for the species. Here, we review these aspects and discuss how evolutionary-imposed anti-homeostatic immune programs are expressed during acute and chronic human diseases, which can be further aggravated in the absence of medical interventions. The relevance of early identification of ancestral biomarkers that predict a shift from protective to deleterious immune outcomes is emphasized.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2022.04.019