Mechanism of lung inflammation associated with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with a number of immune-mediated pathologies in peripheral tissues, termed extra-intestinal manifestations (EIM). The organs affected by EIM include the lung, liver, skin and eyes. IBD-induced respiratory pathologies are amongst the most prevalent comorbidities associated with IBD. Approximately 54% of IBD patients have some form of respiratory pathology. The respiratory pathologies associated with IBD range from subclinical respiratory inflammation to active respiratory disease. Bronchiectasis and chronic bronchitis are the most common respiratory diseases associated with IBD. The mechanism by which IBD can induce respiratory pathologies is unknown, this knowledge gap is partially due to a lack of basic science research in this field. Thus, the aim of this study was to utilize murine models of colitis to investigate the immunological mechanisms by which IBD can induce respiratory inflammation. In this study it was found that the DSS, TNBS and Winnie models of colitis develop pulmonary inflammation that is associated with leucocyte infiltration surrounding the pulmonary vasculature. Pulmonary inflammation in DSS colitis is characterised by neutrophil and monocyte recruitment to the lung. Systemic IL-6 levels were elevated in the DSS colitis model and IL-6 was identified to be a factor that contributes to neutrophil recruitment. It was found that systemic IL-6 mediates neutrophil development in the bone marrow thereby providing the cells required to perpetuate inflammation in the lung. Platelet activating factor receptor (PAFR), IL-1β and CCL2 expression were increased in the lungs of DSS colitis mice. PAFR signalling in the lung induces the expression of IL-1β and the recruitment of neutrophils, PAFR signalling did not induce CCL2 expression. It was found that immunomodulatory factors in the serum of DSS colitis induce IL-1β production and CCL2 gene expression in alveolar macrophage through PAFR signalling. The results from this study identify a number of potential pathogenic factors that may be involved in the development of IBD-induced respiratory pathologies.