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Title: The immunomodulatory role of secretory leucoprotease inhibitor (SLPI) in inflammation
Author: Osbourn, Megan
ISNI:       0000 0004 5368 8662
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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Secretory leucoprotease inhibitor (SLPI) has multifaceted roles in protecting tissues from the damaging effects of inflammation. In addition to its well characterised role as a protease inhibitor, SLPI has been shown to have anti-inflammatory and anti-microbial properties. The therapeutic potential for SLPI as an anti-inflammatory treatment has previously been assessed in chronic inflammatory conditions and has shown promising results in a clinical trial with cystic fibrosis (CF) patients. There is evidence to suggest that SLPI can also inhibit acute inflammation; however the administration of exogenous SLPI as a therapy during the acute inflammatory response has never been investigated. The work presented in this thesis establishes recombinant human SLPI (rhSLPI) as a wide-acting anti-inflammatory following both systemic and pulmonary inflammation induced by bacterial cell surface components. Additionally, rhSLPI was able to reduce a number of inflammatory parameters following pulmonary Pseudomonas aeruginosa infection; however it had no effect on bacterial burden. It was noted that despite reductions in known pro-inflammatory markers, IL-17 was increased following rhSLPI treatment. This IL-17 was shown to be from double negative (ON) T cells, which have been previously reported to play a protective role following pulmonary infection. The importance of SLPI as an inflammatory regulator is established through the increased susceptibility of SLPI knockout (KO) mice to LPS-induced lung inflammation as well as Pseudomonas and Staphylococcus pulmonary infection. Together this gives evidence that SLPI modulates the acute inflammatory response. It should therefore be considered as an anti-inflammatory therapeutic for acute sterile conditions, such as pancreatitis, or acute infections such as that seen in acute respiratory distress syndrome (AROS) patients where it could be combined with antibiotics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available