The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis

Neurosci Biobehav Rev. 2020 May:112:519-541. doi: 10.1016/j.neubiorev.2020.02.002. Epub 2020 Feb 21.


The review synthesised evidence examining the association between a. loneliness with inflammation and b. social isolation with inflammation in adults aged 16 or older from the general population. From an initial 7,400 articles we identified 14 papers that examined loneliness, and 16 that examined social isolation. Qualitative syntheses indicated mixed results, variable study quality, and methodological heterogeneity. Most studies provided associations for C-reactive protein CRP, fibrinogen and Interleukin-6 IL-6, and these results were synthesised using random-effects meta-analyses. There was no association between loneliness with CRP or fibrinogen, but there was a significant association between loneliness and IL-6 for most-adjusted but not least-adjusted analyses. There was also a significant least-adjusted association between social isolation with CRP and fibrinogen, which remained significant for fibrinogen in most-adjusted analyses. There was no association between social isolation with IL-6. Sensitivity analyses indicated that methodological heterogeneity impacted on results. Results indicate that social isolation and loneliness could be linked with systemic inflammation, but more robust methodology is needed to confirm these associations and unpack mechanisms.

Keywords: C-reactive protein; Fibrinogen; Inflammation; Interleukin-6; Loneliness; Social isolation.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • C-Reactive Protein*
  • Fibrinogen*
  • Humans
  • Inflammation / blood*
  • Interleukin-6 / blood*
  • Loneliness*
  • Social Isolation*


  • IL6 protein, human
  • Interleukin-6
  • Fibrinogen
  • C-Reactive Protein