Selective inflammatory propensities in adopted adolescents institutionalized as infants

Melissa L. Engel; Christopher L. Coe; Brie M. Reid; Bonny Donzella; Megan R. Gunnar

doi:10.1016/j.psyneuen.2020.105065

Selective inflammatory propensities in adopted adolescents institutionalized as infants

Melissa L. Engel, Christopher L. Coe, Brie M. Reid, Bonny Donzella, Megan R. Gunnar

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English (US)
Article number	105065
Journal	Psychoneuroendocrinology
Volume	124
DOIs	https://doi.org/10.1016/j.psyneuen.2020.105065
State	Published - Feb 2021

Bibliographical note

Funding Information:
This work was supported by the National Institute of Child Health and Human Development [ R21 HD086312 ] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202 ] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible.

Funding Information:
This work was supported by the National Institute of Child Health and Human Development [R21 HD086312] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

Adolescence
Early life adversity
Inflammation
Institutional care
Sex differences

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title = "Selective inflammatory propensities in adopted adolescents institutionalized as infants",

abstract = "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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note = "Funding Information: This work was supported by the National Institute of Child Health and Human Development [ R21 HD086312 ] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202 ] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible. Funding Information: This work was supported by the National Institute of Child Health and Human Development [R21 HD086312] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

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doi = "10.1016/j.psyneuen.2020.105065",

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N1 - Funding Information: This work was supported by the National Institute of Child Health and Human Development [ R21 HD086312 ] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202 ] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible. Funding Information: This work was supported by the National Institute of Child Health and Human Development [R21 HD086312] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship [NSF Grant No. 00039202] awarded to BMR. All opinions, findings, and conclusions expressed are those of the authors and do not necessarily reflect the views of the NSF. Thanks are due to the recruitment and collection team: Colleen Doyle, Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, and Anna Parenteau, and the phlebotomists at the UM Clinical and Translational Science Institute. We would also like to thank Dr. Carrie DePasquale who stepped in at the last minute to help with the TEMRA path analyses. Last, would like to express our gratitude to the families who make this research possible. Publisher Copyright: © 2020 Elsevier Ltd

PY - 2021/2

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N2 - 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.

AB - 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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Selective inflammatory propensities in adopted adolescents institutionalized as infants

Abstract

Bibliographical note

Keywords

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