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Cytokine regulation of monocytic cell subsets in the peritoneal cavity

Hammond, Victoria 2009. Cytokine regulation of monocytic cell subsets in the peritoneal cavity. PhD Thesis, Cardiff University.

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It is well known that Interleukin (IL)-6 is important in the regulation of both the chemokine directed recruitment and apoptotic removal of neutrophils and lymphocytes (Hurst et al. 2001, McLoughlin et al. 2003, 2005). However little is currently known about the role of IL-6 in governing the phenotype, activation and inflammatory trafficking of monocytic cells. In this thesis, an in vivo model of peritoneal inflammation was utilised in combination with in vitro studies using murine resident peritoneal leukocytes, to determine a role for IL-6 in the regulation of monocytic cell activity and trafficking during inflammation. In this respect, it was shown that resident peritoneal macrophages and dendritic cells (DC) were non-responsive to IL-6 signalling, which in DC was associated with an activation-induced loss of IL-6 receptor. This provides a potential mechanism by which DC are able to remove themselves from the immunosuppressive constraint imposed by IL-6, which is known to maintain immature DC (Park et al. 2004), allowing them to mature into activated DC. Upon activation, resident DC did not display a change in chemokine receptor expression, suggesting that they may remain within the peritoneal cavity and undergo antigen presentation and lymphocyte activation locally. In vivo studies revealed that IL-6 did not regulate the inflammatory trafficking of resident macrophages, DC or recruited circulatory monocytes during acute peritonitis. However upon repeated inflammatory activation, IL-6 directed the increased recruitment of infiltrating monocytes to the peritoneal cavity, implicating them as a contributing factor to the peritoneal tissue damage and fibrosis associated with chronic disease progression. Later studies focused on IL-10, since there is a known interplay that exists between IL-6 and IL-10 (Niemand et al. 2003, Fiorentino et al. 1991, Chernoff et al. 1995). In vivo studies defined an anti-inflammatory role for IL-10, whereby it was responsible for limiting inflammatory leukocyte recruitment via its control of chemokine expression, and the suppression of IL-17A secreting T cell development and recruitment. Therefore the pro-inflammatory and anti-inflammatory roles of IL-6 and IL-10 respectively must be finely balanced to allow competent cell mediated immunity against infection whilst preventing excessive tissue damage associated with disease progression.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
ISBN: 9781303191145
Date of First Compliant Deposit: 30 March 2016
Last Modified: 03 Oct 2014 14:48

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