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Cited by 779Tryptophan and brain disordersAdipokines, Inflammation, and Metabolic DiseasesStress Responses and Cortisol

Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters

Del Giudice, Marco, Gangestad, Steven W.·2018·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2018.02.013
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Abstract

Behavioral researchers have increasingly become interested in the idea that chronic, low-grade inflammation is a pathway through which social and behavioral variables exert long-term effects on health. Much research in the area employs putative inflammatory biomarkers to infer an underlying state of inflammation. Interleukin 6 (IL-6) and C-reactive protein (CRP, whose production is stimulated by IL-6) are arguably the two most commonly assayed biomarkers. Yet, in contrast with near-universal assumptions in the field, discoveries in immunology over the past two decades show that neither IL-6 nor CRP are unambiguous inflammatory markers. IL-6 operates through two distinct signaling pathways, only one of which is specifically upregulated during inflammation; both pathways have a complex range of effects and influence multiple physiological processes even in absence of inflammation. Similarly, CRP has two isoforms, one of which is produced locally in inflamed or damaged tissues. The other isoform is routinely produced in absence of inflammation and may have net anti-inflammatory effects. We propose a functional framework to account for the multiple actions of IL-6 and CRP. Specifically, we argue that both molecules participate in somatic maintenance efforts; hence elevated levels indicate that an organism is investing in protection, preservation, and/or repair of somatic tissue. Depending on the state of the organism, maintenance may be channeled into resistance against pathogens (including inflammation), pathogen tolerance and harm reduction, or tissue repair. The findings and framework we present have a range of potential implications for the interpretation of empirical findings in this area-a point we illustrate with alternative interpretations of research on socioeconomic status, stress, and depression.

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  • Inflammatory response is influenced by multiple factors, such as body mass index, use of tobacco and other psychoactive substances, duration and severity of illness, resistance to antidepressant treatment, other psychiatric comorbidities, unbalanced diet, lack of exercise, and stress or traumatic life events in childhood or adulthood.

    “However, we also need to keep in mind that inflammatory response is influenced by multiple factors, such as body mass index, use of tobacco and other psychoactive substances, duration and severity of illness, resistance to antidepressant treatment, other psychiatric comorbidities, unbalanced diet, lack of exercise, and stress or traumatic life events in childhood or adulthood [27, 29, 39].”

    From Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depressed patients with suicidal behavior: A systematic review (2024) · cites this paper as [39]

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Authors
Del Giudice, M., & Gangestad, S. W.
Affiliations
University of New Mexico (US)
ORCID
Gangestad, Steven W.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2018-05
Volume
70
Pages
61-75
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2018.02.013
OpenAlex
W2792059755
Cited by
779
References
166
Citations by year
2026: 84 · 2025: 131 · 2024: 136 · 2023: 91 · 2022: 121 · 2021: 92 · 2020: 69 · 2019: 39 · 2018: 15
FWCI
4.70
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
interleukin-6, C-reactive protein, inflammatory markers, low-grade inflammation, somatic maintenance, tissue repair, pathogen resistance, pathogen tolerance, harm reduction, social determinants of health, socioeconomic status, stress, depression
MeSH terms
Animals, C-Reactive Protein, Depression, Humans, Inflammation, Social Class, Stress, Psychological, Signal Transduction, Biomarkers, Interleukin-6

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