Stress mediators and immune dysfunction in patients with acute cerebrovascular diseases

PLoS One. 2013 Sep 19;8(9):e74839. doi: 10.1371/journal.pone.0074839. eCollection 2013.


Background: Post-stroke immune depression contributes to the development of infections which are major complications after stroke. Previous experimental and clinical studies suggested that humoral stress mediators induce immune dysfunction. However, prospective clinical studies testing this concept are missing and no data exists for other cerebrovascular diseases including intracerebral hemorrhage (ICH) and TIA.

Methods: We performed a prospective clinical study investigating 166 patients with TIA, ischemic and hemorrhagic stroke. We measured a broad panel of stress mediators, leukocyte subpopulations, cytokines and infection markers from hospital admission to day 7 and on follow-up after 2-3 months. Multivariate regression analyses detected independent predictors of immune dysfunction and bacterial infections. ROC curves were used to test the diagnostic value of these parameters.

Results: Only severe ischemic strokes and ICH increased some catecholamine metabolites, ACTH and cortisol levels. Immunodysfunction was eminent already on hospital admission after large brain lesions with lymphocytopenia as a key feature. None of the stress mediators was an independent predictor of lymphocytopenia or infections. However, lymphocytopenia on hospital admission was detected as an independent explanatory variable of later infections. NIHSSS and lymphocytopenia on admission were excellent predictors of infection.

Conclusions: Our results question the present pathophysiological concept of stress-hormone mediated immunodysfunction after stroke. Early lymphocytopenia was identified as an early independent predictor of post-stroke infections. Absence of lymphocytopenia may serve as a negative predictive marker for stratification for early antibiotic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / metabolism
  • Aged
  • Bacterial Infections / complications
  • Bacterial Infections / diagnosis
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism
  • Biomarkers / metabolism
  • Cerebral Hemorrhage / immunology
  • Cerebral Hemorrhage / metabolism
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / diagnosis
  • Cerebrovascular Disorders / immunology*
  • Cerebrovascular Disorders / metabolism*
  • Female
  • Humans
  • Immunomodulation
  • Ischemia / immunology
  • Ischemia / metabolism
  • Lymphopenia / diagnosis
  • Lymphopenia / immunology
  • Lymphopenia / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • ROC Curve


  • Adrenal Cortex Hormones
  • Biomarkers

Grant support

This work was supported by grants from the Deutsche Forschungsgemeinschaft (VE196/3-1) and the Else Kröner-Fresenius foundation (2012-A118) and by a fellowship of the Daimler-Benz foundation to A.L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.