Advertisement

Current Epidemiology Reports

, Volume 5, Issue 4, pp 407–417 | Cite as

Early Life Socioeconomic Disadvantage and Epigenetic Programming of a Pro-inflammatory Phenotype: a Review of Recent Evidence

  • Amanda M. Simanek
  • Paul L. Auer
Social Epidemiology (A Aiello, Section Editor)
  • 34 Downloads
Part of the following topical collections:
  1. Topical Collection on Social Epidemiology

Abstract

Purpose of Review

A growing body of literature suggests that early life socioeconomic disadvantage (SD) may play a key role in shaping a pro-inflammatory phenotype hypothesized to result from programming of cells of the innate immune system (i.e., monocytes and macrophages) for desensitization to glucocorticoid signaling and exacerbated inflammatory response to immune stimuli, yet understanding of the biologic pathways by which such programming may occur remains limited. The purpose of this review is to discuss the current research supporting the hypothesis that early life SD is associated with a pro-inflammatory phenotype beginning in childhood and highlight recent findings regarding the role that epigenetic programming via DNA methylation (DNAm) specifically, may serve as a biologic mediator of these associations. Gaps in knowledge and recommendations for future research are also discussed.

Recent Findings

Findings regarding the association between early life SD and DNAm of genes that may be involved in shaping a pro-inflammatory phenotype are mixed, but lend some support for epigenetic alterations to genes regulating inflammatory processes as a mediator of this association. Studies which integrate data on DNAm, gene expression, and markers of a pro-inflammatory phenotype beginning early in life and over time are ultimately needed to fully understand the role of epigenetic programming in shaping this adverse immune phenotype in those born into socioeconomically disadvantaged environments.

Summary

Epigenetic programming of a pro-inflammatory phenotype represents a plausible and understudied pathway by which socioeconomic disparities in chronic disease develop across the lifecourse and are perpetuated across generations.

Keywords

Socioeconomic disadvantage Early life Epigenetic modifications Inflammation 

Notes

Compliance with Ethical Standards

Conflict of Interest

Amanda M. Simanek and Paul L. Auer each declare no potential conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    Sheldon C, Denise J-D, Edith C, MK A. Childhood socioeconomic status and adult health. Ann N Y Acad Sci. 2010;1186(1):37–55.CrossRefGoogle Scholar
  2. 2.
    Padmanabhan V, Cardoso RC, Puttabyatappa M. Developmental programming, a pathway to disease. Endocrinology. 2016;157(4):1328–40.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hackman DA, Farah MJ, Meaney MJ. Socioeconomic status and the brain: mechanistic insights from human and animal research. Nat Rev Neurosci. 2010;11(9):651–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Elwenspoek MMC, Kuehn A, Muller CP, Turner JD. The effects of early life adversity on the immune system. Psychoneuroendocrinology. 2017;82:140–54.CrossRefPubMedGoogle Scholar
  5. 5.
    Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving towards a model of behavioral and biological mechanisms. Psychol Bull. 2011;137(6):959–97.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–35.CrossRefPubMedGoogle Scholar
  7. 7.
    Liu RS, Aiello AE, Mensah FK, Gasser CE, Rueb K, Cordell B, et al. Socioeconomic status in childhood and C-reactive protein in adulthood: a systematic review and meta-analysis. J Epidemiol Community Health. 2017;71(8):817–26.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Stringhini S, Batty GD, Bovet P, Shipley MJ, Marmot MG, Kumari M, et al. Association of Lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study. PLoS Med. 2013;10(7):e1001479.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Carroll JE, Cohen S, Marsland AL. Early childhood socioeconomic status is associated with circulating interleukin-6 among mid-life adults. Brain Behav Immun. 2011;25(7):1468–74.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Howe LD, Galobardes B, Sattar N, Hingorani AD, Deanfield J, Ness AR, et al. Are there socioeconomic inequalities in cardiovascular risk factors in childhood, and are they mediated by adiposity? Findings from a prospective cohort study. Int J Obes (2005). 2010;34(7):1149–59.CrossRefGoogle Scholar
  11. 11.
    Pilote L, Lynch JW, Richard H, Almeida N, Benjamin EJ, Murabito JM. Life course socioeconomic position is associated with inflammatory markers: the Framingham offspring study. Soc Sci Med (1982). 2010;71(1):187–95.CrossRefGoogle Scholar
  12. 12.
    Slopen N, Loucks EB, Appleton AA, Kawachi I, Kubzansky LD, Non AL, et al. Early origins of inflammation: an examination of prenatal and childhood social adversity in a prospective cohort study. Psychoneuroendocrinology. 2015;51:403–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang YC, Gerken K, Schorpp K, Boen C, Harris KM. Early life socioeconomic status and adult physiological functioning: a life course examination of biosocial mechanisms. Biodemography Soc Biol. 2017;63(2):87–103.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Jones R, Hardy R, Sattar N, Deanfield JE, Hughes A, Kuh D, et al. Novel coronary heart disease risk factors at 60–64 years and life course socioeconomic position: the 1946 British birth cohort. Atherosclerosis. 2015;238(1):70–6.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    John-Henderson NA, Marsland AL, Kamarck TW, Muldoon MF, Manuck SB. Childhood SES and the occurrence of recent negative life events as predictors of circulating and stimulated levels of Interleukin-6. Psychosom Med. 2016;78(1):91–101.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Stringhini S, Zaninotto P, Kumari M, Kivimäki M, Batty GD. Lifecourse socioeconomic status and type 2 diabetes: the role of chronic inflammation in the English longitudinal study of ageing. Sci Rep. 2016;6:24780.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Castagné R, Delpierre C, Kelly-Irving M, Campanella G, Guida F, Krogh V, et al. A life course approach to explore the biological embedding of socioeconomic position and social mobility through circulating inflammatory markers. Sci Rep. 2016;6:25170.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tabassum F, Kumari M, Rumley A, Lowe G, Power C, Strachan DP. Effects of socioeconomic position on inflammatory and hemostatic markers: a life-course analysis in the 1958 British birth cohort. Am J Epidemiol. 2008;167(11):1332–41.CrossRefPubMedGoogle Scholar
  19. 19.
    • Pedersen JM, Mortensen EL, Christensen DS, Rozing M, Brunsgaard H, Meincke RH, et al. Prenatal and early postnatal stress and later life inflammation. Psychoneuroendocrinology. 2018;88:158–66 This study demonstrates that early life socioeconomic disadvantage (assessed 1 year after birth) is associated with elevated interleukin-6 levels in middle adulthood even after adjustment for maternal characteristics and health behaviors at the time of individual’s birth as well as health behaviors and educational attainment in later life, lending support for the hypothesis that those born into socioeconomic disadvantage may be programmed for chronic inflammation in adulthood. CrossRefPubMedGoogle Scholar
  20. 20.
    Miller GE, Chen E. The biological residue of childhood poverty. Child Dev Perspect. 2013;7(2):67–73.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    • Ehrlich KB, Ross KM, Chen E, Miller GE. Testing the biological embedding hypothesis: is early life adversity associated with a later proinflammatory phenotype? Dev Psychopathol. 2016;28(4pt2):1273–83 This study demonstrates that socioeconomic disadvantage in childhood is associated with membership in a “pro-inflammatory cluster” in childhood that is consistent with a pro-inflammatory phenotype, namely, elevated innate-derived inflammatory response to immune stimuli even in the presence of cortisol which normally inhibits synthesis of pro-inflammatory cytokines. Moreover, the authors identified that membership in this pro-inflammatory cluster was stable over time, supporting the hypothesis that programming of cells of the innate immune system for this phenotype may occur during critical periods of development with long-lasting effects on development of chronic inflammation over time. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wright RJ, Visness CM, Calatroni A, Grayson MH, Gold DR, Sandel MT, et al. Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort. Am J Respir Crit Care Med. 2010;182(1):25–33.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    •• Veru F, Dancause K, Laplante DP, King S, Luheshi G. Prenatal maternal stress predicts reductions in CD4+ lymphocytes, increases in innate-derived cytokines, and a Th2 shift in adolescents: project ice storm. Physiol Behav. 2015;144:137–45 This study demonstrates that in addition to socioeconomic disadvantage experienced during childhood, exposure to socioeconomic disadvantage during the prenatal period may also play an important role in programming of offspring for development of a pro-inflammatory phenotype, thereby providing evidence of a novel pathway by which socioeconomic disparities in health are transmitted across generations. CrossRefPubMedGoogle Scholar
  24. 24.
    Miller G, Chen E. Unfavorable socioeconomic conditions in early life presage expression of proinflammatory phenotype in adolescence. Psychosom Med. 2007;69(5):402–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Miller GE, Chen E, Fok AK, Walker H, Lim A, Nicholls EF, et al. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci U S A. 2009;106(34):14716–21.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    •• Castagné R, Kelly-Irving M, Campanella G, Guida F, Krogh V, Palli D, et al. Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome. Sci Rep. 2016;6:38705 Findings from this study demonstrate that childhood socioeconomic disadvantage is associated with upregulation of a wide range of genes that may serve to regulate inflammatory processes and play an important role in development of a pro-inflammatory phenotype via several key functional pathways including cytokine signaling and MAPK signaling. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lawrence T. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Demetriou CA, van Veldhoven K, Relton C, Stringhini S, Kyriacou K, Vineis P. Biological embedding of early-life exposures and disease risk in humans: a role for DNA methylation. Eur J Clin Investig. 2015;45(3):303–32.CrossRefGoogle Scholar
  29. 29.
    •• Needham BL, Smith JA, Zhao W, Wang X, Mukherjee B, Kardia SL, et al. Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: the multi-ethnic study of atherosclerosis. Epigenetics. 2015;10(10):958–69 This study represents one of a few studies that has examined whether childhood socioeconomic disadvantage is associated with DNA methylation of genes that may be involved in the development of a pro-inflammatory phenotype via both regulation of glucocorticoid signaling and inflammatory processes. Findings lend support for the hypothesis that epigenetic regulation of these processes may play a role in programming individuals for a pro-inflammatory phenotype. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    •• Stringhini S, Polidoro S, Sacerdote C, Kelly RS, Van Veldhoven K, Agnoli C, et al. Life-course socioeconomic status and DNA methylation of genes regulating inflammation. Int J Epidemiol. 2015;44(4):1320–30 This study represents one of a few studies that has examined whether childhood socioeconomic disadvantage is associated with DNA methylation of inflammation-related genes and lend support for the hypothesis that epigenetic programming of inflammatory processes may play a key role in development of a pro-inflammatory phenotype in those born into socioeconomically disavantaged environments, independent of later life factors. CrossRefPubMedGoogle Scholar
  31. 31.
    •• McDade TW, Ryan C, Jones MJ, MacIsaac JL, Morin AM, Meyer JM, et al. Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood. Proc Natl Acad Sci U S A. 2017;114(29):7611–6 This study represents the only study to date which has examined the association between childhood socioeconomic disadvantage, DNA methylation of inflammation-related genes and circulating levels of pro-inflammatory cytokines, thereby shedding light on the role that epigenetic programming may play in explaining the effects of early life socioeconomic disadvantage on development of chronic elevations in systemic inflammation, which is consistent with a pro-inflammatory phenotype. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lam LL, Emberly E, Fraser HB, Neumann SM, Chen E, Miller GE, et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci U S A. 2012;109(Suppl 2):17253–60.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Borghol N, Suderman M, McArdle W, Racine A, Hallett M, Pembrey M, et al. Associations with early-life socio-economic position in adult DNA methylation. Int J Epidemiol. 2012;41(1):62–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Turecki G, Meaney M. Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biol Psychiatry. 2016;79(2):87–96.CrossRefPubMedGoogle Scholar
  35. 35.
    Tyrka AR, Ridout KK, Parade SH. Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: associations in children and adults. Dev Psychopathol. 2016;28(4pt2):1319–31.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Anacker C, O'Donnell KJ, Meaney MJ. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin Neurosci. 2014;16(3):321–33.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Palma-Gudiel H, Córdova-Palomera A, Eixarch E, Deuschle M, Fañanás L. Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis. Epigenetics. 2015;10(10):893–902.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol. 2012;4(3):a006049.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    AW P, Gaby P, Cem G. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223(1):20–38.CrossRefGoogle Scholar
  40. 40.
    Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563–82.CrossRefPubMedGoogle Scholar
  41. 41.
    Ivan Z, Francesca G. Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs). Eur J Immunol. 2012;42(8):1924–31.CrossRefGoogle Scholar
  42. 42.
    Pampel FC, Krueger PM, Denney JT. Socioeconomic disparities in health behaviors. Annu Rev Sociol. 2010;36:349–70.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Bublitz MH, Vergara-Lopez C, Treter MOR, Stroud LR. Lower socioeconomic position in pregnancy is associated with lower diurnal cortisol production and lower birth weight in male infants. Clin Ther. 2016;38(2):265–74.CrossRefPubMedGoogle Scholar
  44. 44.
    Nelson JW, Scammell MK, Hatch EE, Webster TF. Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006. Environ Health. 2012;11:10.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O, McArdle WL, et al. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Hum Mol Genet. 2015;24(8):2201–17.CrossRefPubMedGoogle Scholar
  46. 46.
    Joubert Bonnie R, Felix Janine F, Yousefi P, Bakulski Kelly M, Just Allan C, Breton C, et al. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet. 2016;98(4):680–96.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kundakovic M, Champagne FA. Epigenetic perspective on the developmental effects of bisphenol A. Brain Behav Immun. 2011;25(6):1084–93.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Wilson R, Messaoudi I. The impact of maternal obesity during pregnancy on offspring immunity. Mol Cell Endocrinol. 2015;418(0 2):134–42.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Banik A, Kandilya D, Ramya S, Stünkel W, Chong Y, Dheen S. Maternal factors that induce epigenetic changes contribute to neurological disorders in offspring. Genes. 2017;8(6):150.CrossRefPubMedCentralGoogle Scholar
  50. 50.
    Cao-Lei L, Massart R, Suderman MJ, Machnes Z, Elgbeili G, Laplante DP, et al. DNA methylation signatures triggered by prenatal maternal stress exposure to a natural disaster: project ice storm. PLoS One. 2014;9(9):e107653.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Cao-Lei L, Veru F, Elgbeili G, Szyf M, Laplante DP, King S. DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm. Clin Epigenetics. 2016;8:54.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Chen E, Miller GE, Walker HA, Arevalo JM, Sung CY, Cole SW. Genome-wide transcriptional profiling linked to social class in asthma. Thorax. 2009;64(1):38–43.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Joseph J. Zilber School of Public HealthUniversity of Wisconsin-MilwaukeeMilwaukeeUSA

Personalised recommendations