Selective inflammatory propensities in adopted adolescents institutionalized as infants

•Circulating TNFα levels were elevated in previously institutionalized (PI) youth.•Inflammatory cytokine responses to the PMA/IO cocktail were elevated in PI youth.•Percentage of senescent CD8 T cells mediated the greater PI inflammatory response. This study examined whether early life adversity (EL...

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Veröffentlicht in:Psychoneuroendocrinology 2021-02, Vol.124, p.105065-105065, Article 105065
Hauptverfasser: Engel, Melissa L., Coe, Christopher L., Reid, Brie M., Donzella, Bonny, Gunnar, Megan R.
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creator Engel, Melissa L.
Coe, Christopher L.
Reid, Brie M.
Donzella, Bonny
Gunnar, Megan R.
description •Circulating TNFα levels were elevated in previously institutionalized (PI) youth.•Inflammatory cytokine responses to the PMA/IO cocktail were elevated in PI youth.•Percentage of senescent CD8 T cells mediated the greater PI inflammatory response. This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3–21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.
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This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3–21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. 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This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3–21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.</description><subject>Adolescence</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Cytokines</subject><subject>Early life adversity</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Inflammation</subject><subject>Institutional care</subject><subject>Interleukin-6</subject><subject>Male</subject><subject>Orphanages</subject><subject>Sex differences</subject><subject>T-Lymphocytes</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Young Adult</subject><issn>0306-4530</issn><issn>1873-3360</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkN1KAzEQhYMotlZfofQFts4m3SS9EUX8g4IXKl6GNDvRlO3ukqSF-vRmWVv0yquBOefMz0fIOIdpDjm_XE3bsKtxg_WUAu2aBfDiiAxzKVjGGIdjMgQGPJsVDAbkLIQVAHDJ6SkZMEaFFJIPyfsLVmii2-LE1bbS67WOjd9NWt-0WAcXHYakTHTZtBHLrlYYDNaxa4fo4ia6ptaV--rUrml1Es_JidVVwIufOiJv93evt4_Z4vnh6fZmkZmZyGOmDQcmbMHnDHlRaiuKuZmDENZKK0tLsTRFQQXDmU46QI5ML2m6nhlYlpSNyFU_t90s18mcDvO6Uq13a-13qtFO_VVq96k-mq0SUoJMrEaE9wOMb0LwaA_ZHFSHWq3UHrXqUKsedQqOf28-xPZsk-G6N2D6f-vQq2Ac1gZL5xNyVTbuvx3fmu6X9A</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Engel, Melissa L.</creator><creator>Coe, Christopher L.</creator><creator>Reid, Brie M.</creator><creator>Donzella, Bonny</creator><creator>Gunnar, Megan R.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20210201</creationdate><title>Selective inflammatory propensities in adopted adolescents institutionalized as infants</title><author>Engel, Melissa L. ; Coe, Christopher L. ; Reid, Brie M. ; Donzella, Bonny ; Gunnar, Megan R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-ac6037f5693e65daf759c9077ff8f8df2edc55273e4a65d001e3ab22783c0bd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescence</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Cytokines</topic><topic>Early life adversity</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Inflammation</topic><topic>Institutional care</topic><topic>Interleukin-6</topic><topic>Male</topic><topic>Orphanages</topic><topic>Sex differences</topic><topic>T-Lymphocytes</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Engel, Melissa L.</creatorcontrib><creatorcontrib>Coe, Christopher L.</creatorcontrib><creatorcontrib>Reid, Brie M.</creatorcontrib><creatorcontrib>Donzella, Bonny</creatorcontrib><creatorcontrib>Gunnar, Megan R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychoneuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Engel, Melissa L.</au><au>Coe, Christopher L.</au><au>Reid, Brie M.</au><au>Donzella, Bonny</au><au>Gunnar, Megan R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective inflammatory propensities in adopted adolescents institutionalized as infants</atitle><jtitle>Psychoneuroendocrinology</jtitle><addtitle>Psychoneuroendocrinology</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>124</volume><spage>105065</spage><epage>105065</epage><pages>105065-105065</pages><artnum>105065</artnum><issn>0306-4530</issn><eissn>1873-3360</eissn><abstract>•Circulating TNFα levels were elevated in previously institutionalized (PI) youth.•Inflammatory cytokine responses to the PMA/IO cocktail were elevated in PI youth.•Percentage of senescent CD8 T cells mediated the greater PI inflammatory response. This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3–21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33278786</pmid><doi>10.1016/j.psyneuen.2020.105065</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescence
Adolescent
Adult
Cytokines
Early life adversity
Female
Humans
Infant
Inflammation
Institutional care
Interleukin-6
Male
Orphanages
Sex differences
T-Lymphocytes
Tetradecanoylphorbol Acetate - pharmacology
Tumor Necrosis Factor-alpha
Young Adult
title Selective inflammatory propensities in adopted adolescents institutionalized as infants
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