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Eicosanoid and cytokine responses to bacterial infection

Maleki Toyserkani, Shayda 2018. Eicosanoid and cytokine responses to bacterial infection. PhD Thesis, Cardiff University.
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Abstract

Infectious diseases remain some of the most serious health threats facing the world. The immune system is equipped to initiate a rapid and specific response to foreign invaders of the body, with its ultimate aim being to protect an organism from injury and disease. Eicosanoids, including prostaglandins and leukotrienes, are a family of lipids that play key roles in inflammation including helping leukocytes fight infection. Cells of the innate immune system including tissue macrophages, neutrophils and sentinel dendritic cells are major contributors of local eicosanoids. In mammals an inflammatory insult will result in a cytokine cascade whereby tumour necrosis factor α (TNF-α) is released, followed by interleukin-1β (IL-1β) and then IL-6. Downstream of these cytokines, others are released that serve as potent chemoattractants to induce migration of neutrophils and macrophages to the site of infection. It is known that exposure to varying bacterial components results in a different profile of lipids and cytokines, and by characterising mediator signals it may be possible to define biomarker fingerprints predictive for early bacterial infections. To analyse this, a combination of a targeted lipidomic approach and cytokine immunoassays were employed to identify neutrophil and macrophage responses to individual bacterial components and the whole organism. Work in this thesis has identified potential markers of bacterial infection, such as 12- HETE, 14-HDOHE and TNF-α, which, along with future advances, could be used to develop novel strategies for clinicians, nurses and primary care staff to analyse patients suspected of bacterial infection at the bedside. Work here provides an insight into how the eicosanoid and cytokine storms are generated alongside each other to accompany classic inflammation during specific bacterial infection. The ability to distinguish between species of bacteria causing infection could prove invaluable, reducing the time taken to establish the cause of infection, ultimately leading to better patient outcomes.

Item Type: Thesis (PhD)
Date Type: Submission
Status: Unpublished
Schools: Pharmacy
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: Lipid; Bacteria; Infection; Cytokine; Biomarker; Neutrophil
Date of First Compliant Deposit: 28 January 2019
Last Modified: 28 Jan 2019 11:19
URI: http://orca.cf.ac.uk/id/eprint/118837

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