Sepsis-induced diaphragmatic force loss and failure are associated with an increased exposure to proinflammatory mediators. The septic diaphragm has recently been reported to overexpresse chemokines, including the CC chemokine MCP-1 (monocyte chemoattractant protein-1). This thesis seeks to address the significance of MCP-1 overproduction in diaphragm proinflammatory mediator expression and skeletal muscle contractile function. Neutralization of endogenous MCP-1, produced following administration of LPS, decreased transcription of iNOS, IL-6, IL-1alpha, IL-1beta and MCP-1 in the diaphragm and prevented a decrease in diaphragm force production. Furthermore, exogenous MCP-1 stimulated IL-6 and MCP-1 transcription in primary diaphragm myotubes, and injection of MCP-1 in the healthy EDL muscle led to contractile weakness. Taken together, these results suggest that increased MCP-1 production in the septic diaphragm stimulates proinflammatory mediator production by diaphragm myocytes, contributing to the muscle's contractile dysfunction.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101595 |
| Date | January 2006 |
| Creators | Labbé, Katherine. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | © Katherine Labbé, 2006 |
| Relation | alephsysno: 002588407, proquestno: AAIMR32736, Theses scanned by UMI/ProQuest. |
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