Pulmonary infections in the elderly lead to impaired neutrophil targeting, improved by Simvastatin

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@article{aece036971d344399850aa906b835480,
title = "Pulmonary infections in the elderly lead to impaired neutrophil targeting, improved by Simvastatin",
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.",
keywords = "Neutrophil, immunesenesence , pneumonia , sepsis , statins",
author = "Elizabeth Sapey and Jaimin Patel and Hannah Greenwood and Georgia Walton and Jon Hazeldine and Charendeep Sadhra and Dhruv Parekh and Rachel Dancer and Peter Nightingale and Janet Lord and David Thickett",
year = "2017",
month = nov,
day = "15",
doi = "10.1164/rccm.201704-0814OC",
language = "English",
volume = "196",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "10",

}

RIS

TY - JOUR

T1 - Pulmonary infections in the elderly lead to impaired neutrophil targeting, improved by Simvastatin

AU - Sapey, Elizabeth

AU - Patel, Jaimin

AU - Greenwood, Hannah

AU - Walton, Georgia

AU - Hazeldine, Jon

AU - Sadhra, Charendeep

AU - Parekh, Dhruv

AU - Dancer, Rachel

AU - Nightingale, Peter

AU - Lord, Janet

AU - Thickett, David

PY - 2017/11/15

Y1 - 2017/11/15

N2 - 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.

AB - 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.

KW - Neutrophil

KW - immunesenesence

KW - pneumonia

KW - sepsis

KW - statins

U2 - 10.1164/rccm.201704-0814OC

DO - 10.1164/rccm.201704-0814OC

M3 - Article

VL - 196

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 10

M1 - BLUE_201704-814OC

ER -