Close relationships, inflammation, and health

doi:10.1016/j.neubiorev.2009.09.003

Neuroscience & Biobehavioral Reviews

Volume 35, Issue 1, September 2010, Pages 33-38

https://doi.org/10.1016/j.neubiorev.2009.09.003 Get rights and content

Abstract

Different aspects of personal relationships including social integration, social support, and social conflict have been related to inflammation. This article summarizes evidence linking the quality and quantity of relationships with gene expression, intracellular signaling mechanisms, and inflammatory biomarkers, and highlights the biological and psychological pathways through which close relationships impact inflammatory responses. Relationship conflict and lower social support can effectively modulate proinflammatory cytokine secretion both directly (via CNS/neural/endocrine/immune biobehavioral pathways), and indirectly, by promoting depression, emotional stress responses, and detrimental health behaviors. Accordingly, thorough assessments of health behaviors and attention to key methodological issues are necessary to identify the contributions of relationships to inflammation, and thus we highlight procedural issues to be considered in the design of studies. Despite some notable methodological challenges, the evidence suggests that learning more about how close relationships influence inflammation will provide important new insights into the ways that relationships impact health.

Section snippets

Inflammation and health

Local inflammation is a vital immune response triggered by infection and injury. Inflammatory responses promote the destruction and clearance of viral and bacterial pathogens, and enhance wound healing. Proinflammatory cytokines attract immune cells to sites of infection or injury, activating them to respond to the insult. While acute, local inflammation is beneficial, chronic low grade inflammation may have detrimental health consequences.

Inflammation is a robust and reliable predictor of

Pathways from personal relationships to health: depression, stress, and inflammation

Depression is reliably associated with relationship conflict and lower social support, providing one psychological mechanism through which close relationships influence inflammation (Graham et al., 2007). There is a robust association between inflammation and depression not only in clinically depressed samples, but also in community-based samples (Howren et al., 2009); some non-replications may be due to confounding factors such as body mass index (BMI) or medication use (Glassman and Miller,

Social relationships and inflammation

Different aspects of relationships, including social integration, social support, and social conflict have been related to inflammatory processes. Social relationships impact gene expression, intracellular signaling mechanisms, and inflammatory biomarkers. These associations have been observed across the life span in both healthy participants and individuals with chronic medical conditions.

Three types of research design have been used to study the impact of relationships on inflammation: (1)

Health behaviors and other methodological issues

Supportive relationships can substantially influence inflammation by facilitating health promoting behaviors, while relationship conflict or termination can provoke detrimental health behaviors including less physical activity, disturbed sleep, unhealthy diets, and greater use of alcohol and other drugs (Eng et al., 2005). Thorough assessments of health behaviors and attention to key methodological issues are necessary to identify the contributions of relationship quality and distress to

Experimental design and logistical issues

In contrast to the rapid increase in cortisol and catecholamines, serum IL-6 does not rise immediately in response to a laboratory stressor. Several researchers have suggested that assessment 90–120 min after the stressor initiation may be necessary to observe changes (Pace et al., 2006). Indeed, some studies that have not shown significant changes ended data collection earlier. In this context, blood sample processing cannot wait until data collection is complete, because time passage before

Acknowledgments

Work on this paper was supported in part by NIH grants AG029562, CA126857, CA131029, AT003912, UL1RR025755, and CA16058.

References (53)

B.B. Aggarwal et al.
Inflammation and cancer: how hot is the link?
Biochem. Pharmacol.
(2006)
S.W. Cole
Social regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity
Brain Behav. Immun.
(2008)
M.E. Coussons-Read et al.
Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy
Brain Behav. Immun.
(2007)
P. Dandona et al.
Inflammation: the link between insulin resistance, obesity and diabetes
Trends Immunol.
(2004)
M.C. Davis et al.
Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: implications for fatigue
Brain Behav. Immun.
(2008)
E.S. Ford et al.
Social integration and concentrations of C-reactive protein among US adults
Ann. Epidemiol.
(2006)
A.H. Glassman et al.
Where there is depression, there is inflammation…sometimes!
Biol. Psychiatry
(2007)
J.E. Graham et al.
Close relationships and immunity
M. Hamer et al.
The accumulative effects of modifiable risk factors on inflammation and haemostasis
Brain Behav. Immun.
(2008)
N.A. Harrison et al.
Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity
Biol. Psychiatry
(2009)

C. Kasapis et al.

The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review

J. Am. Coll. Cardiol.

(2005)

E. Lopez-Garcia et al.

Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction

Am. J. Clin. Nutr.

(2004)

E.B. Loucks et al.

Relation of social integration to inflammatory marker concentrations in men and women 70 to 79 years

Am. J. Cardiol.

(2006)

S.K. Lutgendorf et al.

Depression, social support, and beta-adrenergic transcription control in human ovarian cancer

Brain Behav. Immun.

(2009)

G.E. Miller et al.

A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappaB signaling

Biol. Psychiatry

(2008)

J.H. O’Keefe et al.

Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health

J. Am. Coll. Cardiol.

(2008)

S.D. Poppitt et al.

Postprandial response of adiponectin, interleukin-6, tumor necrosis factor-alpha, and C-reactive protein to a high-fat dietary load

Nutrition

(2008)

C.L. Raison et al.

Cytokines sing the blues: inflammation and the pathogenesis of depression

Trends Immunol.

(2006)

T.E. Seeman

Social ties and health: the benefits of social integration

Ann. Epidemiol.

(1996)

P.W. Thavasu et al.

Measuring cytokine levels in blood: importance of anticoagulants, processing, and storage conditions

J. Immunol. Methods

(1992)

P.H. Wirtz et al.

Higher body mass index (BMI) is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following acute psychosocial stress in men

Psychoneuroendocrinology

(2008)

A. Bierhaus et al.

A mechanism converting psychosocial stress into mononuclear cell activation

Proc. Natl. Acad. Sci. U.S.A.

(2003)

L. Brydon et al.

Stress-induced cytokine responses and central adiposity in young women

Int. J. Obes.

(2008)

J.L. Clasey et al.

The use of anthropometric and dual-energy X-ray absorptiometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women

Obes. Res.

(1999)

S.W. Cole et al.

Social regulation of gene expression in human leukocytes

Genome Biol.

(2007)

E.S. Costanzo et al.

Psychosocial factors and interleukin-6 among women with advanced ovarian cancer

Cancer

(2005)

Cited by (352)

Social connectedness, functional capacity, and longevity: A focus on positive relations with others
2024, Social Science and Medicine
A large literature links social connectedness to health, but there is growing recognition of considerable nuance in the ways social connectedness is defined, assessed, and associated with health.
This study centers on positive relations with others – a measure derived from philosophical notions of the components of a “good life” – and the extent to which it predicts functional limitations and mortality using data from the national, longitudinal Mid-Life in the United States (MIDUS) study. We also assess whether these associations are independent of two common measures of social connectedness: social integration and social support.
Data on social connectedness came from the first wave of MIDUS (1994–1996), self-reported functional limitations were from the first (MIDUS 1) and third (MIDUS 3; 2013–2014) waves, and mortality data through 2022 were obtained from the National Death Index.
Linear regression analyses showed that higher scores on positive relations with others predicted significantly less increase in functional limitations over time, and logistic regression models showed reduced probability of onset of functional limitations between MIDUS 1 and MIDUS 3 in those scoring higher on positive relations with others. Mortality was also significantly lower in those with higher scores on positive relations with others. All models adjusted for demographic and health characteristics, and all associations were robust to the inclusion of social integration and social support in the models.
These results show that positive relations with others, a component of a well-lived life that describes sustained investment in social relationships that are mutual and trusting, is associated with two key health outcomes in aging adults: functional limitations and longevity. That these associations are independent of social integration and social support suggests a unique role for this formulation of social connectedness in the health of aging adults.
Understanding the health effects of caregiving stress: New directions in molecular aging
2023, Ageing Research Reviews
Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers’ health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16^INK4a, and epigenetic age could help to reconcile mixed literature on caregiving’s sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes –together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.
Partner relationship quality and IL-6:IL-10 trajectories from pregnancy to a year after-birth
2023, Brain, Behavior, and Immunity
Inflammatory activity during pregnancy and the postpartum period shifts systematically due to pregnancy progression, delivery, and postpartum recovery. Factors that deregulate inflammatory activity increase the risk for adverse pregnancy outcomes and slower postpartum recovery. The IL-6:IL-10 or TNF-α:IL-10 ratio is potentially one way to capture peripheral inflammatory regulation; higher values indicate that anti-inflammatory IL-10 is less effective at regulating pro-inflammatory TNF-α or IL-6, skewing towards maladaptive pro-inflammatory profiles. Associations between partner relationship quality and IL-6:IL-10 or TNF-α:IL-10 trajectories during pregnancy and the postpartum period have not been assessed. The purpose of this study was to test whether partner relationship quality (support, conflict) is associated with attenuated IL-6, IL-10, TNF-α, TNF-α:IL-10 or IL-6:IL-10 trajectories from the third trimester to the postpartum period.
A sample of 162 women from the Healthy Babies Before Birth study reported on partner relationship quality (support and conflict) using the Social Support Effectiveness Questionnaire during the third trimester. Plasma samples were collected in the third trimester and at 1-, 6- and 12-months postpartum, and assayed for TNF-α, IL-6 and IL-10. Associations between both indicators of relationship quality (support and conflict) and TNF-α, IL-6, IL-10, IL-6:IL-10, TNF-α:IL-10 trajectories were tested using multi-level modelling, controlling for sociodemographic, pregnancy and health variables.
Partner support interacted with time to predict IL-6:IL-10 trajectories, linear: b = -0.176, SE = 0.067, p =.010, quadratic: b = 0.012, SE = 0.005, p =.009. Lower partner support was associated with steeper increases in IL-6:IL-10 from the third trimester to 6 months postpartum, followed by steeper decreases in IL-6:IL-10 from 6 months postpartum to a year after birth. Partner conflict was not associated with IL-6:IL-10 levels at study entry, b = 0.233, SE = 0.219, p =.290, or over time, p’s > 0.782. Neither indicator of partner relationship quality was associated with TNF-α, IL-6, IL-10, or TNF-α:IL-10 trajectories, p’s > 0.205.
Lower partner support may be associated with reduced moderation of IL-6 by IL-10 between pregnancy and a year postpartum, with possible consequences for maternal health and well-being.
Associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms throughout childhood
2023, Brain, Behavior, and Immunity
Maternal immune activation is a potential mechanism underlying associations between maternal stress during pregnancy and offspring mental health problems. This study examined associations between prenatal maternal stress, maternal inflammation during pregnancy, and children’s internalizing and externalizing symptoms from 3 to 10 years of age, and whether maternal inflammation mediated the associations between prenatal maternal stress and children’s internalizing and externalizing symptoms.
This study comprised 4,902 mother–child dyads in the Generation R study. Prenatal maternal stress was assessed using self-reported data collected during pregnancy and analyzed as a latent variable consisting of four stress domains. Maternal inflammation during pregnancy was assessed using serum concentrations of C-reactive protein (CRP) measured at a median of 13.5 weeks’ gestation. Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist (CBCL) by maternal report at ages 3 years, 5 years, and 10 years; paternal-reported CBCL data were also available at 3 years and 10 years.
Prenatal maternal stress was associated with maternal-reported internalizing and externalizing symptoms of the child at 3, 5, and 10 years of age, and with paternal-reported internalizing and externalizing symptoms at 3 and 10 years. Prenatal maternal stress was associated with maternal CRP concentrations prior to, but not after, covariate adjustment. Maternal CRP concentrations during pregnancy were associated with paternal-reported internalizing symptoms of offspring at 10 years of age prior to, but not after, covariate adjustment. There was no evidence that CRP concentrations mediated the associations between prenatal maternal stress and children’s internalizing or externalizing symptoms.
Maternal stress during pregnancy is associated with higher levels of internalizing and externalizing symptoms in children, but this association is not because of differences in maternal immune activation linked to maternal stress. Replication of these findings in other cohorts is required; examination of other biomarkers or variation in immune activity during pregnancy would also benefit from further exploration.
A perinatal coparenting intervention: Effects of a randomized trial on parent cardiometabolic risk and self-reported health
2023, Biological Psychology
The transition to parenthood is a common yet stressful experience faced by many young and midlife adults, and the risk of cardiometabolic conditions also begins to rise at this time. Consequently, parenthood represents an opportune time to intervene with adults to support their psychological and physical health.
We examined whether the benefits of the Family Foundations program, a perinatal preventative intervention promoting positive coparenting, extend beyond documented mental health and family relationship outcomes to better cardiometabolic risk factors among parents.
We analyzed data from 183 couples (n = 366 participants) who, eight years prior, were randomly assigned to the 9-session perinatal preventative intervention program or a control condition. We collected dried blood spots to measure C-reactive protein (CRP), interleukin-6 (IL-6), and cholesterol; parents also reported on their self-rated health.
Randomization to the intervention condition was associated with lower cholesterol (B=−.081, p = .049). Among parents who demonstrated more negative communication styles at pretest (during pregnancy), the intervention was further associated with better self-rated health (B=.181, p = .018). Participation in the intervention program was also marginally associated with lower CRP (B=−.261, p = .077), particularly among mothers (B=−.428, p = .076).
These findings indicate that coparenting-focused interventions, such as Family Foundations, can lead to benefits beyond psychosocial and behavioral outcomes, and suggest that Family Foundations may improve parents’ longer-term physical health, with potentially more benefits among couples who demonstrated more negative communication styles during pregnancy.
Assessment of the level of social support and associated factors among cancer patients in the comprehensive cancer center at Ethiopia: Ordinal logistic regression analysis level of social support and associated factors among cancer patients
2023, Heliyon
Cancer is a serious and common disease, which had a substantial problem in the social status of patients. There was no empirical evidence on the effect of cancer on social support.
This study aimed to determine the level of social support among cancer patients in a comprehensive cancer center in Ethiopia.
An institution-based cross-sectional study was done. About 386 study participants who were selected through systematic random sampling involved in the study. Training and close supervision and monitoring were done. The collected data were analyzed using SPSS-25. Descriptive statistics and Chi-square test were done. Ordinal bivariate and multivariate logistic regression were done to show the net effect of independent variables on the dependent variable. Model fitting information, the goodness of test, and the test of parallel line assumption test of the ordinal logistic regression model were carried out.
A total of 386 study subjected were included in the final analysis. The poor, moderate, and strong levels of social support among cancer patients were found to be 45.3%, 34.2%, and 20.5% respectively. The mean score of social support among cancer patients was 10.4 ± 2.6SD. Age, Marital status, residence, educational status, stage III were found to be significant factors for the level of social support.
and recommendation: The level of poor, moderate, and strong social support was found to be 45.3%, 34.2 and 20.5 respectively. Emphasis should be given to those cancer patients who had poor social support, and frequent social status assessment should be done.

View all citing articles on Scopus

¹: Department of Psychology, The Ohio State University, 193 McCampbell Hall, 1581 Dodd Drive, Columbus, OH 43210-1228, USA.

View full text

ReviewClose relationships, inflammation, and health

Abstract

Section snippets

Inflammation and health

Pathways from personal relationships to health: depression, stress, and inflammation

Social relationships and inflammation

Health behaviors and other methodological issues

Experimental design and logistical issues

Acknowledgments

Biochem. Pharmacol.

Brain Behav. Immun.

Brain Behav. Immun.

Trends Immunol.

Brain Behav. Immun.

Ann. Epidemiol.

Biol. Psychiatry

Brain Behav. Immun.

Biol. Psychiatry

J. Am. Coll. Cardiol.

Am. J. Clin. Nutr.

Am. J. Cardiol.

Brain Behav. Immun.

Biol. Psychiatry

J. Am. Coll. Cardiol.

Nutrition

Trends Immunol.

Ann. Epidemiol.

J. Immunol. Methods

Psychoneuroendocrinology

A mechanism converting psychosocial stress into mononuclear cell activation

Proc. Natl. Acad. Sci. U.S.A.

Stress-induced cytokine responses and central adiposity in young women

Int. J. Obes.

The use of anthropometric and dual-energy X-ray absorptiometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women

Obes. Res.

Social regulation of gene expression in human leukocytes

Genome Biol.

Psychosocial factors and interleukin-6 among women with advanced ovarian cancer

Cancer

Review
Close relationships, inflammation, and health