An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness
Abstract
Background It is assumed that both social stress and chronological age increase the risk of chronic illness, in part, through their effect on systemic inflammation. Unfortunately, observational studies usually employ single-marker measures of inflammation (e.g., Interleukin-6, C-reactive protein) that preclude strong tests for mediational effects. Objective The present study investigated the extent to which the effects of socioeconomic disadvantage and age on onset of chronic illness is mediated by dominance of the innate (inflammatory) over the acquired (antiviral) components of the immune system. Methods We assessed inflammation using the ratio of inflammatory to antiviral cell types (ITACT Ratio). This approach provided a stronger test of evolutionary arguments regarding the effect of social stress on chronic inflammation than is the case with cytokine measures, and afforded an opportunity to replicate findings obtained utilizing mRNA. We used structural equation modeling and longitudinal data from a sample of 100 middle-age African American women to perform our analyses. Results Dominance of inflammatory over antiviral cell activity was associated with each of the eight illnesses included in our chronic illness measure. Both socioeconomic disadvantage and age were also associated with inflammatory dominance. Pursuant to the central focus of the study, the effects of socioeconomic adversity and age on increased illness were mediated by our measure of inflammatory dominance. The indirect effect of these variables through inflammatory cell profile was significant, with neither socioeconomic disadvantage nor age showing a significant association with illness once the impact of inflammatory cell profile was taken into account. Conclusions First, the analysis provides preliminary validation of a new measure of inflammation that is calculated based on the ratio of inflammatory to antiviral white blood cells. Second, our results support the hypothesis that socioeconomic disadvantage and chronological age increase risk for chronic illness in part through their effect on inflammatory processes.
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The CTRA has been proposed as a potential predictive biomarker for disease risk and pathogenesis related to inflammatory and interferon response alterations, and may have utility as an indicator of AD progression.
“The CTRA has been proposed as a potential predictive biomarker for disease risk and pathogenesis related to diseases impacted by inflammatory and interferon response alterations including cancer and heart disease [96], and may have utility as an indicator of AD progression [21].”
From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [96]
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- Authors
- Simons, R. L., Lei, M.-K., Beach, S. R. H., Barr, A. B., Cutrona, C. E., Gibbons, F. X., & Philibert, R. A.
- Affiliations
- University of Georgia (US)
- University at Buffalo, State University of New York (US)
- Iowa State University (US)
- University of Connecticut (US)
- University of Iowa (US)
- Corresponding author
- Simons, Ronald L.
- ORCID
- Venue
- Social Science & Medicine
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 185
- Pages
- 158-165
- ISSN
- 0277-9536 (ISSN-L)
- OpenAlex
- W2602184032
- Cited by
- 38
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 4
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Social Science & Medicine (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL118045)
- National Institute on Drug Abuse (R21DA034457)
- National Institute of Mental Health (R01MH62699, R01MH62666)
- Topics
- Social Sciences › Health › Health disparities and outcomes
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- chronic disease, social adversity, socioeconomic deprivation, age, systemic inflammation, innate immunity, antiviral immunity, immune cell composition, mediation, African American women, middle age (human life stage), social stress
- MeSH terms
- Age Factors, Cells, Chronic Disease, Humans, Inflammation, Socioeconomic Factors, Stress, Psychological, Biomarkers, Patient Acuity, Social Norms
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