Close relationships, inflammation, and health
Open accessAbstract
KIECOLT-GLASER, J.K., J-P. Gouin, and L. Hantsoo, Close Relationships, Inflammation, and Health. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX, 2009.- 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.
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- Premisecitation
There is a robust association between inflammation and depression in clinically depressed samples and in community-based samples.
“There is a robust association between inflammation and depression not only in clinically depressed samples, but also in community-based samples”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Howren et al., 2009 source
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In a genome-wide DNA microarray study, genes under-expressed by socially isolated individuals involved anti-inflammatory response elements and genes over-expressed involved proinflammatory response elements, compared to less isolated individuals.
“in a genome-wide DNA microarray study, genes under-expressed by socially isolated individuals involved anti-inflammatory response elements and genes over-expressed involved proinflammatory response elements, compared to individuals who reported less social isolation”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cole et al., 2007 source
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Psychosocial stress can directly provoke proinflammatory cytokine production in the absence of infection or injury.
“Psychosocial stress can directly provoke proinflammatory cytokine production in the absence of infection or injury.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bierhaus et al., 2003 source
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Depression may sensitize the inflammatory response, promoting larger cytokine increases in response to stressors or antigen challenge.
“there is some evidence that depression may sensitize the inflammatory response, thus effectively promoting larger cytokine increases in response to stressors or antigen challenge”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Glaser et al., 2003
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- cites Pace et al., 2006 source
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Chronic inflammation has been suggested as one key biological mechanism that may fuel declines in physical function leading to frailty, disability, and death.
“chronic inflammation has been suggested as one key biological mechanism that may fuel declines in physical function leading to frailty, disability, and, ultimately, death”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ershler and Keller, 2000 source
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The inverse relationship between social integration and IL-6/CRP was observed only among older men.
“However, this relationship was observed only among older men”
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CRP and proinflammatory cytokines IL-1, IL-6, and TNF-alpha are prognostic for cardiovascular disease, type II diabetes, arthritis, osteoporosis, Alzheimer's disease, and periodontal disease.
“C-reactive protein (CRP) and proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α) are prognostic for cardiovascular disease, type II diabetes, arthritis, osteoporosis, Alzheimer's disease, and periodontal disease”
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Norepinephrine-dependent adrenergic stimulation activates NF-kB, which activates gene expression of several inflammatory mediators.
“Norepinephrine-dependent adrenergic stimulation activates transcription factor nuclear factor kappa B (NF-κB), an intracellular signaling molecule that activates gene expression of several inflammatory mediators”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bierhaus et al., 2003 source
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- Interpretationreasoning
Relationship conflict and lower social support can modulate proinflammatory cytokine secretion indirectly by promoting depression, emotional stress responses, and detrimental health behaviors.
“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.”
Quote in the paperSubstantial claim - Interpretationreasoning
Norepinephrine's responsivity to stress provides a direct route for translating interpersonal stress into inflammation.
“norepinephrine's well-documented responsivity to stress (Kiecolt-Glaser et al., 1997) provides a direct route for translating interpersonal stress into inflammation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 1997 source
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- Interpretationnone given
Relationship conflict and lower social support can modulate proinflammatory cytokine secretion directly via CNS, neural, endocrine, and immune biobehavioral pathways.
“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.”
Quote in the paperSubstantial claim - Premisecitation
Disturbed sleep, a common correlate of depression and stress, promotes IL-6 production.
“disturbed sleep, a common correlate of depression and stress, promotes IL-6 production”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vgontzas et al., 2004 source
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The size of the effect of marriage on CRP was comparable to that of other traditional risk factors such as smoking, hypertension, and obesity.
“the size of the effect of marriage on CRP was comparable to that of other traditional risk factors such as smoking, hypertension, and obesity”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sbarra, 2009 source
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- Premisecitation
Different aspects of personal relationships, including social integration, social support, and social conflict, have been related to inflammation.
“Different aspects of personal relationships including social integration, social support, and social conflict have been related to inflammation.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Depression and stressful interpersonal experiences contribute to both acute and chronic proinflammatory cytokine production.
“Through these pathways, depression and stressful interpersonal experiences contribute to both acute and chronic proinflammatory cytokine production”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Inflammation is a robust and reliable predictor of all-cause mortality in older adults.
“Inflammation is a robust and reliable predictor of all-cause mortality in older adults.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning
By promoting depression and emotional stress responses, relationship conflict and lower social support can modulate proinflammatory cytokine secretion both directly and indirectly.
“By promoting depression and emotional stress responses, relationship conflict and lower social support can effectively modulate secretion of proinflammatory cytokines both directly (via CNS/neural/endocrine/immune biobehavioral pathways), and indirectly, through behavioral changes.”
Quote in the paperSubstantial claim - Interpretationcitation
Some non-replications of the inflammation-depression association may be due to confounding factors such as BMI or medication use.
“some non-replications may be due to confounding factors such as body mass index (BMI) or medication use”
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- cites Howren et al., 2009 source
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Modest sleep deficits produced significant overall IL-6 increases in the following 24 hours in young, healthy, normal sleepers.
“Modest sleep deficits produced significant overall IL-6 increases in the following 24 hours in young, healthy, normal sleepers”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vgontzas et al., 2004 source
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Among socially isolated individuals, diminished regulation of leukocyte trafficking by cortisol was observed compared to more socially integrated individuals.
“Among socially isolated individuals, diminished regulation of leukocyte trafficking by cortisol was observed, compared to more socially integrated individuals”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cole, 2008 source
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- Interpretationcitation
Diminished sensitivity to the anti-inflammatory properties of glucocorticoids provides one potential mechanism through which chronic interpersonal stressors such as caregiving promote chronic low grade inflammation.
“Diminished sensitivity to the anti-inflammatory properties of glucocorticoids provides one potential mechanism through which chronic interpersonal stressors such as caregiving promote chronic low grade inflammation.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
CRP levels above 3 mg/L indicate high relative risk for cardiovascular disorder, independent of other known risk factors.
“CRP levels above 3 mg/L indicate high relative risk for cardiovascular disorder, independent of other known risk factors”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ridker, 2009 source
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In ovarian cancer patients, more frequent use of instrumental support and greater perceptions of closeness and intimacy in personal relationships were associated with lower plasma IL-6.
“In ovarian cancer patients, the more frequent use of instrumental support and greater perceptions of closeness and intimacy in personal relationships were associated with lower plasma IL-6.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Women with greater central adiposity produced larger inflammatory responses to a laboratory stress task than their leaner counterparts.
“women with greater central adiposity produced larger inflammatory responses to a laboratory stress task than their leaner counterparts”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Brydon et al., 2008 source
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IL-6 levels were more than twice as high 10 hours after a breakfast high in saturated fat compared to a healthier alternative.
“IL-6 levels were more than twice as high 10 hours after a breakfast high in saturated fat compared to a healthier alternative”
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Many medications directly and indirectly influence inflammation.
“Many medications directly and indirectly influence inflammation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2007 source
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When physical or cardiorespiratory fitness is assessed rigorously and objectively by maximal exercise testing, fitness is inversely associated with inflammation, even after adjusting for confounds including age, smoking, medications, and visceral fat.
“When physical or cardiorespiratory fitness is assessed rigorously and objectively by maximal exercise testing, fitness is inversely associated with inflammation, even after adjusting for confounds including age, smoking, medications, and visceral fat”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kasapis and Thompson, 2005 source
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Adolescents who reported more daily interpersonal stressors had higher CRP plasma levels than those with less interpersonal stress.
“adolescents who reported more daily interpersonal stressors had higher CRP plasma levels than those with less interpersonal stress”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fuligni et al., 2009 source
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Among older women, trusting and satisfying relationships with others and concerns with others' welfare were related to lower IL-6.
“Among older women, trusting and satisfying relationships with others, and concerns with others’ welfare were related to lower IL-6”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Friedman et al., 2005 source
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In a six-year longitudinal study, caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers.
“a six-year longitudinal study revealed that caregivers’ average rate of increase in IL-6 was about four times as large as that of noncaregivers”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2003 source
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NF-kB was overexpressed in ovarian tumors of patients who reported both high levels of depression and low levels of social support, compared to counterparts without these risk factors.
“the proinflammatory transcription factor Nf-κB, was overexpressed in ovarian tumors of patients who reported both high levels of depression and low levels of social support, compared to their counterparts without these risk factors”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lutgendorf et al., 2009 source
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Obesity may exaggerate inflammatory responses to stressors.
“obesity may exaggerate inflammatory responses to stressors”
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Smoking is reliably associated with heightened inflammatory responses.
“Smoking is reliably associated with heightened inflammatory responses”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hamer and Stamatakis, 2008
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Among adults diagnosed with rheumatoid arthritis, greater daily interpersonal stress was related to higher LPS-stimulated IL-6 production.
“Among adults diagnosed with rheumatoid arthritis, greater daily interpersonal stress was also related to higher LPS-stimulated IL-6 production”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Davis et al., 2008 source
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Proinflammatory responses to meals high in saturated fats are exaggerated by obesity.
“proinflammatory responses to meals high in saturated fats are exaggerated by obesity, pushing elevated levels even higher”
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Community women who were caregivers had higher plasma IL-6 levels than women anticipating a housing relocation or community controls, despite being 6 to 9 years younger.
“Community women who were caregivers had higher plasma IL-6 levels than either women who were anticipating a housing relocation or community controls, despite the fact that caregivers were 6 to 9 years younger than women in the other two groups”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lutgendorf et al., 1999 source
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Higher intakes of a Westernized diet have been associated with higher CRP, IL-6, E-selectin, sICAM-1, and sVCAM-1.
“Higher intakes of a “Westernized” diet (red and processed meats, sweets, desserts, French fries, and refined grains) have been associated with higher CRP, IL-6, E-selectin, sICAM-1, and sVCAM-1”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lopez-Garcia et al., 2004 source
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In a six-month longitudinal study of adolescent females, greater interpersonal stress was associated with larger LPS-stimulated IL-6 production and bigger NF-kB increases over time.
“In a six-month longitudinal study of adolescent females, greater interpersonal stress was associated with larger lipopolysaccharide (LPS)-stimulated IL-6 production and bigger NFκB increases over time”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2009 source
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- Interpretationcitation
The IL-6 differences described by multiple laboratories provide one viable mechanism that could explain caregivers' substantial differences in mortality.
“The IL-6 differences described by multiple laboratories provide one viable mechanism that could explain caregivers’ substantial differences in mortality”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Schulz and Beach, 1999 source
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Obesity has been characterized as a state of chronic inflammation because of elevated plasma levels of IL-6, TNF-alpha, and CRP.
“Obesity has been characterized as a state of chronic inflammation because of the elevated plasma levels of IL-6, TNF-α, and CRP”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dandona et al., 2004 source
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Glucocorticoid inhibition of inflammatory cytokine production following acute stress was lower in men with a higher BMI than in their leaner counterparts.
“glucocorticoid inhibition of inflammatory cytokine production following acute stress was lower in men with a higher BMI than in their leaner counterparts”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wirtz et al., 2008 source
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Disrupted sleep can dysregulate proinflammatory cytokine production, altering both normal diurnal patterns and total production.
“Disrupted sleep can dysregulate proinflammatory cytokine production, altering both the normal diurnal patterns and total production”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vgontzas et al., 2004 source
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People who describe themselves as physically active have lower levels of inflammation than their sedentary counterparts.
“People who describe themselves as physically active have lower levels of inflammation than their sedentary counterparts”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kasapis and Thompson, 2005 source
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Pregnant women reporting lower levels of social support during their third trimester had higher CRP throughout the pregnancy compared to women with better social support.
“Pregnant women reporting lower levels of social support during their third trimester had higher CRP throughout the pregnancy, compared to women with better social support”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Coussons-Read et al., 2007 source
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Hostile behavior during marital conflict augments adverse immune and endocrine changes, including enhanced norepinephrine production.
“hostile behavior during marital conflict augments adverse immune and endocrine changes, including enhanced norepinephrine production”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser and Newton, 2001 source
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Time passage before samples are processed and frozen can substantially influence cytokine concentrations.
“time passage before samples are processed and frozen can substantially influence cytokine concentrations”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Thavasu et al., 1992 source
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Moderate alcohol intake is associated with lower levels of systemic inflammatory markers than non-drinking and heavy drinking.
“Moderate alcohol intake is associated with lower levels of systemic inflammatory markers than non-drinking and heavy drinking.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hamer and Stamatakis, 2008
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Serum IL-6 does not rise immediately in response to a laboratory stressor; assessment 90-120 minutes after stressor initiation may be necessary to observe changes.
“serum IL-6 does not rise immediately in response to a laboratory stressor. Several researchers have suggested that assessment 90-120 minutes after the stressor initiation may be necessary to observe changes”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Pace et al., 2006 source
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- Interpretationcitation
Relationships characterized by hostility and conflict could have negative health consequences.
“Thus, relationships characterized by hostility and conflict could have negative health consequences.”
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In large longitudinal studies of initially healthy individuals, elevated IL-6 and CRP levels independently predicted risk of cardiovascular events compared to other risk factors.
“In large longitudinal studies of initially healthy individuals, elevated IL-6 (mean 1.81 pg/mL vs. 1.46 pg/mL) and CRP levels (median 4.2 mg/L vs. 2.8 mg/L) independently predicted risk of cardiovascular events, compared to other risk factors”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Ridker et al., 2000a
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- cites Ridker et al., 2000b
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- Interpretationnone given
Correlational studies suggest that social isolation, lack of social integration, and interpersonal conflict are associated with higher IL-6 and CRP.
“Correlational studies suggest that social isolation, lack of social integration, and interpersonal conflict are associated with higher IL-6 and CRP.”
Quote in the paperSubstantial claim - Premisecitation
Caregiving for a child with cancer has been associated with diminished inhibition of LPS-stimulated IL-6 production following glucocorticoid administration.
“Caregiving for a child with cancer has been associated with diminished inhibition of LPS-stimulated IL-6 production following glucocorticoid administration”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2002 source
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- Interpretationreasoning
Night or swing shift workers may provide unrepresentative data because of altered diurnal cycles.
“Night or swing shift workers may provide unrepresentative data because of altered diurnal cycles.”
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PremisecitationAmong older adults, married men had lower CRP levels than previously married men, as well as married and unmarried women.
“Among older adults, married men had lower CRP levels than previously married men, as well as married and unmarried women”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sbarra, 2009 source
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PremisecitationDepression is reliably associated with relationship conflict and lower social support.
“Depression is reliably associated with relationship conflict and lower social support, providing one psychological mechanism through which close relationships influence inflammation”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Graham et al., 2007
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PremisecitationPharmacologically-induced inflammation can produce symptoms of depression, indicating that the relationship between inflammation and depression is bidirectional.
“Findings that pharmacologically-induced inflammation can produce symptoms of depression indicate that the relationship between inflammation and depression is bidirectional.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dantzer et al., 2008 source
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PremisecitationThe CRP differences by marital status were not explained by mood, stress, loneliness, or social support, and none of these variables moderated the association.
“Notably, these CRP differences were not explained by mood, stress, loneliness, or social support, and none of these variables moderated the association between marital status and CRP levels”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sbarra, 2009 source
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PremisecitationSocial integration, as assessed by marital status, number of close friends and relatives, and participation in religious activities, clubs, and voluntary associations, is inversely related to plasma levels of IL-6 and CRP.
“Social integration, as assessed by marital status, number of close friends and relatives, and participation in religious activities, clubs, and voluntary associations was inversely related to plasma levels of IL-6 and CRP.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationDepression and stress contribute to a greater risk for infection, prolonged infectious episodes, and delayed wound healing.
“depression and stress contribute to a greater risk for infection, prolonged infectious episodes, and delayed wound healing”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Glaser and Kiecolt-Glaser, 2005
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PremisecitationEven after their spouse's death, bereaved spousal caregivers' mean annual rate of change in IL-6 did not differ from current caregivers, and these patterns were not explained by differences in health or medication status.
“Even after their spouse's death, bereaved spousal caregivers’ mean annual rate of change in IL-6 did not differ from current caregivers, and these patterns of change were not explained by differences in health or medication status.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2003 source
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PremisecitationDietary intake and/or supplements like omega-3 and curcumin can impact inflammation as well as mood.
“dietary intake and/or supplements like omega-3 and curcumin can also impact inflammation as well as mood”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2007 source
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PremisecitationAcute exercise transiently boosts production and release of IL-6 from skeletal muscles; the IL-6 released during physical activity inhibits TNF-alpha production and induces IL-10 production.
“acute exercise transiently boosts production and release of IL-6 from skeletal muscles; the IL-6 that is released during physical activity inhibits TNF-α production and induces IL-10 production, one of exercise's anti-inflammatory mechanisms”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kasapis and Thompson, 2005 source
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PremisecitationCompared to similar older adults without caregiving responsibilities, caregivers have an increased risk for infectious disease and delayed wound healing.
“Compared to similar older adults without caregiving responsibilities, caregivers have an increased risk for infectious disease (evidenced by poorer vaccine responses) as well as delayed wound healing”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Glaser and Kiecolt-Glaser, 2005
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PremisecitationGenes underexpressed by family cancer caregivers included glucocorticoid response elements, while genes overexpressed included NF-kB response elements, compared to noncaregiving controls.
“genes underexpressed by family cancer caregivers included glucocorticoid response elements, while genes overexpressed included NF-κB response elements, compared to noncaregiving controls”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2008 source
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PremisecitationAmong individuals caring for a family member with cancer, CRP increased and glucocorticoid sensitivity decreased in the year following the first radiotherapy treatment.
“Among individuals who were caring for a family member with cancer, CRP increased and glucocorticoid sensitivity decreased in the year following the first radiotherapy treatment”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rohleder et al., 2009 source
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PremisecitationLess hostile couples showed roughly the same increment in IL-6 over 24 hours following either a social support or conflict interaction (65% vs. 70%), while IL-6 production for more hostile couples jumped from 45% to 113%.
“less hostile couples showed roughly the same increment in IL-6 over 24 hours following either a social support or conflict interaction (65% vs. 70%), while IL-6 production for the more hostile couples jumped from 45% to 113%”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2005 source
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PremisecitationCaregivers' social networks shrink over the course of caregiving; bereaved caregivers' self-rated loneliness remains similar to that of current caregivers for several years or more after the death of the impaired spouse, contributing to enduring IL-6 differences.
“Caregivers’ social networks shrink over the course of caregiving; bereaved caregivers’ self-rated loneliness remains similar to that of current caregivers for several years or more after the death of the impaired spouse, undoubtedly contributing to the enduring IL-6 differences”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kiecolt-Glaser et al., 2003 source
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PremisecitationEpidemiological studies have linked social isolation, low social support, and high levels of social conflict with morbidity and mortality, and inflammation provides one obvious mechanism.
“Epidemiological studies have linked social isolation, low social support, and high levels of social conflict with morbidity and mortality, and inflammation provides one obvious mechanism”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Graham et al., 2007
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PremisecitationAge was significantly correlated with IL-6 in caregivers but not controls, suggesting older caregivers may be at risk for a rapid transition into frailty syndrome.
“age was significantly correlated with IL-6 in caregivers but not controls, suggesting that older caregivers may be at risk for a rapid transition into what has been termed the frailty syndrome”
Quote in the paperSubstantial claim0 of 1 sources checked- cites von Kanel et al., 2006 source
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InterpretationreasoningDementia caregiving strains family relationships, resulting in depression as well as inflammation.
“In sum, dementia caregiving strains family relationships, resulting in depression as well as inflammation.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationSupportive 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.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Eng et al., 2005 source
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PremisecitationAdipocytes are capable of producing and secreting IL-6 and TNF-alpha; up to 30% of IL-6 may be derived from adipose tissue.
“adipocytes (fat cells) are capable of producing and secreting IL-6 and TNF-α; up to 30% of IL-6 may be derived from adipose tissue”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dandona et al., 2004 source
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PremisecitationIL-6 and TNF-alpha have distinct diurnal cycles; normal IL-6 values at 9:00 PM are more than twice as large as those at 9:00 AM.
“Both IL-6 and TNF-α have distinct diurnal cycles, e.g., normal IL-6 values at 9:00 PM are more than twice as large as those at 9:00 AM”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vgontzas et al., 2004 source
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The paper relies on this without support.
The cited studies' findings are valid and can be generalized to the populations and contexts discussed in the review.
“This article summarizes evidence linking inflammation and health, and highlights the pathways through which close personal relationships impact inflammatory responses.”
The paper relies on this without support.
The biomarkers IL-6 and CRP adequately reflect inflammatory processes relevant to health outcomes.
“C-reactive protein (CRP) and proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α) are prognostic for cardiovascular disease, type II diabetes, arthritis, osteoporosis, Alzheimer's disease, and periodontal disease”
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These effects of naturally occurring social stressors on inflammation are detected for both acute and chronic forms of life stress and are particularly strong for social stressors involving conflict, threat, isolation, and rejection.
“These effects have been detected for both acute and chronic forms of life stress and are particularly strong for social stressors involving conflict, threat, isolation, and rejection”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Kiecolt-Glaser, Gouin, & Hantsoo, 2010
The ‘Pathways From Personal Relationships To Health’ section (page unavailable) says stressful interpersonal experiences contribute to acute and chronic inflammatory cytokine production. ‘Social Relationships and Inflammation’ links conflict and isolation to inflammatory markers, but the copy does not establish that effects are particularly strong for these stressors relative to others, or specifically address threat and rejection. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNaturally occurring social stressors in adolescence and adulthood are associated with elevated levels of inflammatory activity.
“There is also a large body of research demonstrating that naturally occurring social stressors in adolescence and adulthood are associated with elevated levels of inflammatory activity.”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Kiecolt-Glaser, Gouin, & Hantsoo, 2010
Social bonding probably supports brain health via core neuroendocrine pathways influencing many brain and body functions.
“As seen in Figure 1, social bonding likely contributes to brain health through primary neuroendocrine pathways that affect numerous brain and bodily functions.6,38”
From Why the cognitive ‘fountain of youth’ may be upstream: pathways to dementia risk and resilience through social connectedness (2022) · cites this paper as [38]
In humans, stress correlates with memory problems and quicker cognitive decline in early-stage ADRD.
“In humans, stress is associated with memory impairment and faster rates of cognitive decline among those with early stage ADRD.38,46,47”
From Why the cognitive ‘fountain of youth’ may be upstream: pathways to dementia risk and resilience through social connectedness (2022) · cites this paper as [38]
Chronic inflammation is a potent driver of disease.
“Chronic inflammation is a potent driver of disease.35”
From Social Media Use and Its Link to Physical Health Indicators (2022) · cites this paper as [35]
Such inflammation is a potent driver of diseases such as cardiovascular disease, cancers, and diabetes.
“Such inflammation is a potent driver of diseases such as cardiovascular disease, cancers, and diabetes (Emerging Risk Factors Collaboration, 2010; Kiecolt-Glaser et al., 2010; Uchino et al., 2018; Zhou et al., 2012).”
From Social media use and systemic inflammation: The moderating role of self-esteem (2021) · cites this paper as Kiecolt-Glaser et al., 2010
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“Such inflammation is a potent driver of diseases such as cardiovascular disease, cancers, and diabetes (Emerging Risk Factors Collaboration, 2010; Kiecolt-Glaser et al., 2010; Uchino et al., 2018; Zhou et al., 2012).”
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- Authors
- Kiecolt-Glaser, J. K., Gouin, J.-P., & Hantsoo, L.
- Affiliations
- The Ohio State University (US)
- ORCID
- Hantsoo, Liisa
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 35
- Issue
- 1
- Pages
- 33-38
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC2891342
- OpenAlex
- W2015323877
- Semantic Scholar
- 98bf02fd8382d82e2ae76e58e9d79c566bbc8d35
- Cited by
- 480
- References
- 55
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 23 · 2023: 24 · 2022: 29 · 2021: 43 · 2020: 43 · 2019: 39 · 2018: 33 · 2017: 30 · 2016: 26 · 2015: 27 · 2014: 34 · 2013: 35 · 2012: 27
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG029562, R21AG025732, AG029562)
- National Cancer Institute (CA16058, CA126857, R01CA126857, CA131029, R01CA131029, P30CA016058)
- National Center for Research Resources (UL1RR025755)
- National Center for Complementary and Integrative Health (R21AT003912, AT003912)
- Topics
- Social Sciences › Psychology › Social Psychology › Attachment and Relationship Dynamics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- close relationships, inflammation, social support, social conflict, relationship quality, inflammatory cytokines, gene expression, inflammatory markers, depression, emotional stress, health behavior, social integration
- MeSH terms
- Alcohol Drinking, Animals, Behavior, Chronic Disease, Depression, Female, Health Status, Humans, Inflammation, Interpersonal Relations, Male, Motor Activity, Smoking, Stress, Psychological, Adiposity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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