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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:646201 |
| Date | January 2015 |
| Creators | Patel, Jaimin Mukesh |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/5837/ |
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