Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults
Open accessAbstract
Increased production of peripheral cytokines and other pro-inflammatory markers has been linked to psychiatric disorders such as major depressive disorder and post-traumatic stress disorder. Recent research has pointed to early-life stress, particularly childhood maltreatment, as an independent and preventable risk factor for systemic inflammation in adulthood. Some data suggest that adults with a history of childhood maltreatment exhibit a heightened inflammatory response to acute stress challenge. To further elucidate the relationship between childhood maltreatment and pro-inflammatory cytokine production, we examined plasma IL-6 response to the Trier Social Stress Test (TSST) in 69 healthy adult subjects without depression or post-traumatic stress disorder. Serial plasma IL-6 concentrations were measured during a standardized psychosocial stressor in n=19 subjects with moderate-severe childhood maltreatment (MAL), and n=50 controls without maltreatment (CTL), as indicated by self-ratings on the childhood trauma questionnaire (CTQ). CTQ total scores were positively correlated with overall change in IL-6 response, as well as the maximum IL-6 concentration during the TSST. Greater acute IL-6 release and higher IL-6 concentrations over time were observed for the MAL group relative to the CTL group. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult physical and mental health. The results of this preliminary study warrant further investigation in a larger sample.
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Positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (a pro-inflammatory phenotype) in adulthood.
“There is growing evidence suggesting that positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (i.e., a pro-inflammatory phenotype) in adulthood (101, 164–172).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [169]
The Introduction describes early-life stress as an apparent independent risk for systemic inflammation and a pro-inflammatory phenotype in adulthood. The study’s Discussion reports heightened peripheral IL-6 response to acute stress after childhood maltreatment, but its Results find no significant association with baseline IL-6. The paper therefore supports altered inflammatory response, not the claim of long-term, low-grade inflammatory excess. (LLM, conf=0.88)
Experimental — accuracy not yet measuredExperiencing more early life stress, as assessed by the Childhood Trauma Questionnaire, was unrelated to baseline levels of IL-6 but strongly associated with greater increases in IL-6 in response to the TSST.
“Experiencing more early life stress, as assessed by the Childhood Trauma Questionnaire (CTQ; Bernstein et al., 1994), was unrelated to baseline levels of IL-6 but strongly associated with greater increases in IL-6 in response to the TSST.”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Carpenter et al., 2010
Participants who experienced moderate to severe early life stress exhibited significantly greater IL-6 responses to the TSST than their counterparts with little or no early life stress, although these groups had similar baseline levels of IL-6.
“although these groups had similar baseline levels of IL-6, participants who experienced moderate to severe early life stress exhibited significantly greater IL-6 responses to the TSST than their counterparts with little or no early life stress”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Carpenter et al., 2010
Childhood adversity is associated with alterations in the inflammatory arm of the immune system.
“and the inflammatory arm of the immune system (Carpenter et al., 2010; Danese et al., 2011; Danese, Pariante, Caspi, Taylor, & Poulton, 2007; Slopen, Kubzansky, McLaughlin, & Koenen, 2013; Taylor, Lehman, Kiefe, & Seeman, 2006).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Carpenter et al., 2010
Cumulative childhood maltreatment is associated with exaggerated inflammatory responses to acute stress.
“Cumulative childhood maltreatment is associated with exaggerated inflammatory responses to acute stress (Carpenter et al., 2010)”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Carpenter et al., 2010
IL-6 is a consistently elevated biomarker of chronic stress in long-term caregivers, early life adversity, and depressed individuals that attempted suicide.
“IL-6 is a consistently elevated biomarker of chronic stress in long-term caregivers [8], early life adversity [9], and depressed individuals that attempted suicide [10].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [9]
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- Authors
- Carpenter, L. L., Gawuga, C. E., Tyrka, A. R., Lee, J. K., Anderson, G. M., & Price, L. H.
- Affiliations
- Brown University (US)
- Butler Hospital (US)
- Yale University (US)
- Corresponding author
- Carpenter, Linda L
- Venue
- Neuropsychopharmacology
- Published
- 2010-09-29
- Volume
- 35
- Issue
- 13
- Pages
- 2617-2623
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2978751
- OpenAlex
- W2006656085
- Cited by
- 464
- References
- 51
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 28 · 2023: 28 · 2022: 30 · 2021: 33 · 2020: 35 · 2019: 30 · 2018: 50 · 2017: 28 · 2016: 29 · 2015: 30 · 2014: 33 · 2013: 29 · 2012: 27
- FWCI
- 26.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH068767)
- National Institute of General Medical Sciences (R25GM083270)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- interleukin-6, acute stress response, childhood adversity, child abuse, Trier Social Stress Test, systemic inflammation, inflammatory cytokines, childhood trauma, healthy adults, psychosocial stress
- MeSH terms
- Adolescent, Adult, Anxiety, Depression, Female, Humans, Male, Middle Aged, Stress, Psychological, Interleukin-6, Adult Survivors of Child Abuse, Self Report
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