Use this URL to cite or link to this record in EThOS:
Title: Exaggerated neutrophil immunosenescence in sepsis and its potential modification with simvastatin
Author: Patel, Jaimin Mukesh
ISNI:       0000 0004 5361 2051
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
Availability of Full Text:
Access from EThOS:
Access from Institution:
Sepsis remains a common reason for hospital admission and is associated with a high mortality especially in the elderly. Neutrophils are one of the primary immune cells involved in the elimination of pathogens; however also contribute to the pathogenesis of multi-organ failure in sepsis. Previous studies have demonstrated an age-related decline in neutrophil migration and phagocytosis suggesting this as a mechanism for the poorer outcomes observed from sepsis in the elderly. Observational studies suggest that HMG-CoA reductase inhibitors (statins) are associated with improved outcomes from sepsis and potentially modulate neutrophil function. This thesis demonstrates that high dose (80mg) simvastatin improved the migration of neutrophils in the healthy elderly without affecting other key neutrophil functions, such as phagocytosis and reactive oxygen species production (ROS). Studies in patients with sepsis, demonstrated that circulating neutrophils displayed features of immune-paresis and failed to migrate, but were activated with increased phagocytosis and ROS. This was accompanied by reduced neutrophil extracellular trap (NET) formation and delayed late apoptosis. The use of in-vitro simvastatin failed to modulate migration, whilst ROS and NET production was reduced by simvastatin. Simvastatin remains a potential immune-modulating drug for treating early infection in the elderly.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology ; RC Internal medicine