The role of tumour necrosis factor alpha in acute inflammation of human lung tissue

Abstract

This thesis has assessed the role of TNFα in acute inflammation in human lung tissue. TNFα has previously been shown to play an important role in many chronic inflammatory diseases, and is now accepted as an important therapeutic target in rheumatoid arthritis, inflammatory bowl disease and severe asthma. This thesis aims to investigate the contribution of cytokines, in particular TNFα, in the acute inflammatory response and how they may be affected by disease. This thesis illustrates that TNFα is the key cytokine in the acute inflammatory response, initiated by LPS, in human lung tissue. In addition we had demonstrated that the main cellular sources of TNFα in acute inflammation are alveolar macrophages and mast cells. An important clinical finding of this study is that patients with COPD and current smokers have an exaggerated TNFα response, which would lead to the elevated release of pro-inflammatory mediators and extracellular matrix destruction during inflammation. We have also verified that IL-10 can modulate TNFα expression in human lung tissue, and we have also demonstrated that patients with COPD produce lower levels of IL-10 in response to an LPS challenge. This study therefore highlights the role of TNFα and IL-10 in the progression of COPD and provides important future therapeutic targets for the disease.

We have also demonstrated that the decline in protein expression with disease could result from the elevated metabolic turnover due to the enhanced oxidation of proteins in COPD patients. In particular we have shown that oxidised HSA, an important antioxidant, is turned over more rapidly in human lung tissue.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata