Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women

Psychoneuroendocrinology. 2012 Nov;37(11):1801-9. doi: 10.1016/j.psyneuen.2012.03.016. Epub 2012 Apr 12.


Loneliness is a predictor of mortality and increased cardiovascular morbidity. Inflammation is a potential pathway through which loneliness might impact health. The aim of the study was to investigate the relationship between loneliness and inflammatory interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra) and monocyte chemotactic protein-1 (MCP-1) responses to standardized mental stress. A secondary purpose was to evaluate whether individual variations in cortisol responses influenced the hypothesised relationship between loneliness and inflammation. Saliva samples and blood were taken from 524 healthy middle-aged men and women from the Whitehall II cohort at baseline, immediately after the stress tasks and 45min later. Loneliness was measured using the revised UCLA loneliness scale. Greater loneliness was associated with larger IL-6 (p=0.044) and IL-1Ra (p=0.006) responses to psychological stress and higher MCP-1 (p<0.001) levels in women, independently of age, grade of employment, body mass index and smoking status. No associations were observed in men. Cortisol responsivity was inversely related to loneliness in women, with the odds of being a cortisol responder decreasing with increased loneliness independently of covariates (p=0.008). The impact of loneliness on health in women may be mediated in part through dysregulation of inflammatory and neuroendocrine systems.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chemokine CCL2 / blood
  • Female
  • Humans
  • Hydrocortisone / analysis
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin-6 / blood
  • Loneliness / psychology*
  • Male
  • Middle Aged
  • Neurosecretory Systems / physiology
  • Saliva / chemistry
  • Sex Factors
  • Stress, Psychological / blood
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology


  • CCL2 protein, human
  • Chemokine CCL2
  • IL6 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Hydrocortisone