, Volume 214, Issue 1, pp 309–317 | Cite as

Hypothalamic–pituitary–adrenal axis activity and upper respiratory tract infection in young children transitioning to primary school

  • Julie M. Turner-Cobb
  • Lorna Rixon
  • David S. Jessop
original investigation



We have previously reported an increase in salivary cortisol in a cohort of 4-year-old children transitioning to primary school. We hypothesised that increased cortisol in response to this acute naturalistic stress in early development may be immunostimulatory and associated with positive health outcomes.


We tested this hypothesis by measuring upper respiratory tract infection (URI) across the first 6 months of school, in relation to salivary cortisol at the end of the second week following school transition


Seventy children supplied morning and evening saliva samples for cortisol assay. Children were psychologically assessed for temperament and behavioural adaptation. Symptoms of URI were recorded in diary form, and variables relating to URI occurrence, duration and severity were assessed.


Children with higher evening cortisol at school transition experienced significantly fewer episodes of URI over the following 6 months. Diurnal cortisol change was negatively correlated with number of illnesses across the 6 months, indicating an association between a greater decline in cortisol across the day and a greater number of colds. URI severity was associated with the greatest resistance to URI infection in children who were less socially isolated and who had a smaller diurnal change in cortisol across the day.


Our results showing that higher cortisol is associated with lower URI may be explained by proposing that increased cortisol in response to the naturalistic stress of school transition may prime the immune system to develop resistance to URI at this critical stage of a child’s development.


Cortisol Immune Respiratory Infection Children School Stress Saliva 



This research was funded by a grant from the Economic and Social Research Council (ESRC), UK (#RES-000-23-0141) awarded to the principal investigator, Julie M. Turner-Cobb. The authors would like to express their gratitude to the children, their parents, teachers and schools who took part in this study. The authors have no conflicts of interest with any aspect of this study or its funders.


  1. Ahadi SA, Rothbart MK, Ye R (1993) Children’s temperament in the US and China: similarities and differences. Eu J Personality 7:359–377CrossRefGoogle Scholar
  2. Armario A, Marti O, Valles A, Dal-Zotto S, Ons S (2004) Long-term effects of a single exposure to immobilization on the hypothalamic–pituitary–adrenal axis: neurobiologic mechanisms. Ann NY Acad Sci 1018:162–172PubMedCrossRefGoogle Scholar
  3. Ball TM, Holberg CJ, Aldous MB, Martinez FD, Wright AL (2002) Influence of attendance at day care on the common cold from birth through 13 years of age. Arch Ped Adolesc Med 156:121–126Google Scholar
  4. Barber AE, Coyle SM, Marano MA, Fischer E, Calvano SE, Fong Y, Moldawer LL, Lowry SF (1993) Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol 150:1999–2006PubMedGoogle Scholar
  5. Besedovsky HO, del Rey A (2002) Immune-neuro-endocrine interactions: facts and hypotheses. Front Horm Res 29:1–14PubMedCrossRefGoogle Scholar
  6. Boyce WT, Adams S, Tschann JM, Cohen F, Wara D, Gunnar MR (1995) Adrenocortical and behavioral predictors of immune responses to starting school. Pediatr Res 38:1009–1017PubMedCrossRefGoogle Scholar
  7. Chrousos GP (2000) Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. J Allergy Clin Immunol 106:S275–S291PubMedCrossRefGoogle Scholar
  8. Chryssanthopoulou CC, Turner-Cobb JM, Lucas A, Jessop D (2005) Childcare as a stabilizing influence on HPA-axis functioning: a re-evaluation of maternal occupational patterns and familial relations. Dev Psychobiol 47:354–368PubMedCrossRefGoogle Scholar
  9. Clow A, Thorn L, Evans P, Hucklebridge F (2004) The awakening cortisol response: methodological issues and significance. Stress 7:29–37PubMedCrossRefGoogle Scholar
  10. Coe CL, Lubach GR (2003) Critical periods of special health relevance for psychoneuroimmunology. Brain Behav Immun 17:3–12PubMedCrossRefGoogle Scholar
  11. Cohen S, Tyrrell DA, Smith AP (1993) Negative life events, perceived stress, negative affect, and susceptibility to the common cold. J Pers Soc Psychol 64:131–140PubMedCrossRefGoogle Scholar
  12. Cohen S, Hamrick N, Rodriguez MS, Feldman PJ, Rabin BS, Manuck SB (2002) Reactivity and vulnerability to stress-associated risk for upper respiratory illness. Psychosom Med 64:302–310PubMedCrossRefGoogle Scholar
  13. Cowan PA, Cowan CP (1990) Becoming a family: research and intervention. In: Sigel E, Brody IE (eds) Methods of family research: biographies of research projects, vol. 1: normal families. Lawrence Earlbaum Associates, Hillsdale, pp 1–51Google Scholar
  14. Cowan PA, Cowan CP, Schulz MC, Heming G (1994) Prebirth to preschool family factors in children’s adaptation to kindergarten. In: Parke RD, Kellam SG (eds) Exploring family relationships with other social contexts. Lawrence Erlbaum Associates, Hillsdale, pp 75–114Google Scholar
  15. Davis EP, Donzella B, Krueger WK, Gunnar MR (1999) The start of a new school year: individual differences in salivary cortisol response in relation to child temperament. Dev Psychobiol 35:188–196PubMedCrossRefGoogle Scholar
  16. Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16:300–317PubMedCrossRefGoogle Scholar
  17. Dhabhar FS, McEwen BS (1997) Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav Immun 11:286–306PubMedCrossRefGoogle Scholar
  18. Dhabhar FS, Saul AN, Daugherty C, Holmes TH, Bouley DM, Oberyszyn TM (2010) Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma. Brain Behav Immun 24:127–137PubMedCrossRefGoogle Scholar
  19. Evans PD, Edgerton N (1991) Life events and mood as predictors of the common cold. Brit J Med Psychol 64:35–44PubMedGoogle Scholar
  20. Falagas ME, Karamanidou C, Kastoris AC, Karlis G, Rafailidis PI (2010) Psychosocial factors and susceptibility to or outcome of acute respiratory tract infections. Int J Tuberc Lung Dis 14:141–148PubMedGoogle Scholar
  21. Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5:243–251PubMedCrossRefGoogle Scholar
  22. Gow R, Thomson S, Rieder M, Van Uum S, Koren G (2010) An assessment of cortisol analysis in hair and its clinical applications. Forensic Sci Int 196:32–37PubMedCrossRefGoogle Scholar
  23. Haavet OR, Straand J, Saugstad OD, Grünfeld B (2004) Illness and exposure to negative life experiences in adolescence: two sides of the same coin? A study of 15-year-olds in Oslo, Norway. Acta Paediatr 93:405–411PubMedCrossRefGoogle Scholar
  24. Hamrick N, Cohen S, Rodriguez MS (2002) Being popular can be healthy or unhealthy: stress, social network diversity, and incidence of upper respiratory infection. Health Psychol 21:294–298PubMedCrossRefGoogle Scholar
  25. Harbuz MS, Chover-Gonzalez A, Gibert-Rahola J, Jessop DS (2002) Protective effect of prior acute immune challenge, but not footshock, on inflammation in the rat. Brain Behav Immun 16:439–449PubMedCrossRefGoogle Scholar
  26. Hazeldine J, Arlt W, Lord JM (2010) Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol 120:127–136PubMedCrossRefGoogle Scholar
  27. Howell DC (2002) Statistical methods for psychology. Thomson Learning, DuxburyGoogle Scholar
  28. Jessop DS, Turner-Cobb JM (2008) Measurement and meaning of salivary cortisol: a focus on health and disease in children. Stress 11:1–14PubMedCrossRefGoogle Scholar
  29. Jessop DS, Dallman MF, Fleming D, Lightman SL (2001) Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab 86:4109–4114PubMedCrossRefGoogle Scholar
  30. Johnson VK, Cowan PA, Cowan CP (1999) Children’s classroom behavior: the unique contribution of family organization. J Fam Psychol 13:355–371CrossRefGoogle Scholar
  31. Lien L, Haavet OR, Thoresen M, Heyerdahl S, Bjertness E (2007) Mental health problems, negative life events, perceived pressure and the frequency of acute infections among adolescents. Results from a cross-sectional, multicultural, population-based study. Acta Paediatr 96:301–306PubMedCrossRefGoogle Scholar
  32. Lutgendorf SK, Costanzo ES (2003) Psychoneuroimmunology and health psychology: an integrative model. Brain Behav Immun 17:225–232PubMedCrossRefGoogle Scholar
  33. McEwen BS (1998) Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci 840:33–44PubMedCrossRefGoogle Scholar
  34. McEwen BS, Stellar E (1993) Stress and the individual. Mechanisms leading to disease. Arch Intern Med 153:2093–2101PubMedCrossRefGoogle Scholar
  35. McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM (1997) The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev 23:79–133PubMedCrossRefGoogle Scholar
  36. Marshall GD Jr (2009) Identifying the stress-susceptible patient at risk for inflammatory diseases: an interdisciplinary approach. Expert Rev Clin Immunol 5:119–121PubMedCrossRefGoogle Scholar
  37. Richards LJ, Chover-Gonzalez A, Harbuz MS, Jessop DS (2006) Protective effects of endotoxin in a rat model of chronic inflammation are accompanied by suppressed secretion of pro-inflammatory cytokines and biphasic alteration in hypothalamo-pituitary-adrenal axis activity. J Neuroendocrinol 18:875–882PubMedCrossRefGoogle Scholar
  38. Rosenberger PH, Ickovics JR, Epel E, Nadler E, Jokl P, Fulkerson JP, Tillie JM, Dhabhar FS (2009) Surgical stress-induced immune cell redistribution profiles predict short-term and long-term postsurgical recovery. A prospective study. J Bone Joint Surg Am 91:2783–2794PubMedCrossRefGoogle Scholar
  39. Rothbart MK, Ahadi SA, Hershey K, Fisher PA (2001) Investigations of temperament at three to seven years: the Children’s Behavior Questionnaire. Child Dev 72:1394–1408PubMedCrossRefGoogle Scholar
  40. Sephton SE, Sapolsky RM, Kraemer H, Spiegel D (2000) Diurnal cortisol rhythm as a predictor of breast cancer survival. J Nat Cancer Inst 92:994–1000PubMedCrossRefGoogle Scholar
  41. Stone AA, Bovbjerg DH, Neale JM, Napoli A, Valdimarsdottir H, Cox D, Hayden FG, Gwaltney JM Jr (1992) Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events. Behav Med 18:115–120PubMedCrossRefGoogle Scholar
  42. Straub RH, Dhabhar FS, Bijlsma JW, Cutolo M (2005) How psychological stress via hormones and nerve fibers may exacerbate rheumatoid arthritis. Arthr Rheum 52:16–26CrossRefGoogle Scholar
  43. Tilders FJ, Schmidt ED, Hoogendijk WJ, Swaab DF (1999) Delayed effects of stress and immune activation. Baillieres Best Pract Res Clin Endocrinol Metab 13:523–540PubMedCrossRefGoogle Scholar
  44. Turner-Cobb JM (2005) Psychological and stress hormone correlates in early life: a key to HPA-axis dysregulation and normalisation. Stress 8:47–57PubMedCrossRefGoogle Scholar
  45. Turner Cobb JM, Steptoe A (1996) Psychosocial stress and susceptibility to upper respiratory tract illness in an adult population sample. Psychosom Med 58:404–412Google Scholar
  46. Turner Cobb JM, Steptoe A (1998) Psychosocial influences on upper respiratory infectious illness in children. J Psychosom Med 45:319–330CrossRefGoogle Scholar
  47. Turner-Cobb JM, Rixon L, Jessop DS (2008) A prospective study of diurnal cortisol responses to the social experience of school transition in four-year-old children: anticipation, exposure, and adaptation. Dev Psychobiol 50:377–389PubMedCrossRefGoogle Scholar
  48. Valles A, Marti O, Armario A (2003) Long-term effects of a single exposure to immobilization stress on the hypothalamic–pituitary–adrenal axis: transcriptional evidence for a progressive desensitization process. Eur J Neurosci 18:1353–1361PubMedCrossRefGoogle Scholar
  49. Watamura SE, Donzella B, Alwin J, Gunnar MR (2003) Morning-to-afternoon increases in cortisol concentrations for infants and toddlers at child care: age differences and behavioral correlates. Child Dev 74:1006–1020PubMedCrossRefGoogle Scholar
  50. Wiegers GJ, Reul JM, Holsboer F, de Kloet ER (1994) Enhancement of rat splenic lymphocyte mitogenesis after short term preexposure to corticosteroids in vitro. Endocrinology 135:2351–2357PubMedCrossRefGoogle Scholar
  51. Yeager MP, Rassias AJ, Pioli PA, Beach ML, Wardwell K, Collins JE, Lee HK, Guyre PM (2009) Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin. Crit Care Med 37:2727–2732PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Julie M. Turner-Cobb
    • 1
  • Lorna Rixon
    • 1
  • David S. Jessop
    • 2
  1. 1.Department of PsychologyUniversity of BathBathUK
  2. 2.Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE)University of BristolBristolUK

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