Pulmonary infections in the elderly lead to impaired neutrophil targeting, which is improved by simvastatin

Elizabeth Sapey, Jaimin Patel, Hannah Greenwood, Georgia Walton, Jon Hazeldine, Charendeep Sadhra, Dhruv Parekh, Rachel Dancer, Peter Nightingale, Janet Lord, David Thickett

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
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Abstract

Rationale: Dysregulated neutrophil functions are described with age and sepsis. Statins are associated with improved infection survival in some observational studies but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro.
Objective: To assess neutrophil migratory accuracy with age during respiratory infections and determine if and how a statin intervention could alter these blunted responses.
Methods. Migratory accuracy of blood neutrophils from young (aged<35) and old (aged>60) patients in health, during a lower respiratory tract infection (LRTI), pneumonia (CAP) and pneumonia associated sepsis (S-CAP) was assessed with and without simvastatin. In vitro results were confirmed in a double-blinded randomised clinical trial in healthy elders. Cell adhesion markers were assessed.
Results: In vitro neutrophil migratory accuracy in the elderly deteriorated as the severity of the infectious pulmonary insult increased, without recovery at six weeks. Simvastatin rescued neutrophil migration with age and during mild-moderate infection, at high dose in older adults, but not during more severe sepsis. Confirming in vitro results, high dose (80mg) simvastatin improved neutrophil migratory accuracy without impeding other neutrophil functions in a randomised, double-blinded clinical trial in healthy elders. Simvastatin modified surface adhesion molecule expression and activity, facilitating accurate migration in the elderly. 
Conclusions: Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections.
Original languageEnglish
Pages (from-to)1325–1336
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume196
Issue number10
Early online date28 Jun 2017
DOIs
Publication statusPublished - 15 Nov 2017

Keywords

  • Neutrophil
  • immunesenesence
  • pneumonia
  • sepsis
  • statins

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