Development of severe colitis is associated with lung inflammation and pathology

Abstract

Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic relapsing diseases that affect the gastrointestinal tract, most commonly the colon. A link between the gut and the lung is suggested since patients with IBD have an increased susceptibility for chronic inflammatory lung disease. Furthermore, in the absence of overt lung disease, IBD patients have worsened lung function and more leukocytes in sputum than healthy individuals, highlighting a conduit between the gut and lung in disease. To study the gut-lung axis in the context of IBD, we used TCRδ-/- mice, which are highly susceptible to dextran sulfate sodium (DSS) due to the importance of γδ T cells in maintenance of barrier integrity. After induction of experimental colitis using DSS, the lungs of TCRδ-/- mice exhibited signs of inflammation and mild emphysema, which was not observed in DSS-treated C57BL/6 mice. Damage to the lung tissue was accompanied by a large expansion of neutrophils in the lung parenchyma and an increase in alveolar macrophages in the lung wash. Gene expression analyses showed a significant increase in Csf3, Cxcl2, Tnfa, and Il17a in lung tissue in keeping with neutrophil infiltration. Expression of genes encoding reactive oxygen species enzymes and elastolytic enzymes were enhanced in the lungs of both C57BL/6 and TCRδ-/- mice with colitis. Similarly, surfactant gene expression was also enhanced, which may represent a protective mechanism. These data demonstrate that severe colitis in a susceptible genetic background is sufficient to induce lung inflammation and tissue damage, providing the research community with an important tool for the development of novel therapeutics aimed at reducing co-morbidities in IBD patients.

Pulmonary embolism induces pneumonia‐like lung injury beyond pulmonary infarction

“…The incidence of pneumonia lesions on CT images was significantly higher in the PE group (36.9%) compared to the DVT group (26.3%) ( p < 0.0001) (Table 2). Previous studies have suggested that chronic lung disease, chronic digestive disease, trauma, and tumors could induce pulmonary inflammation 22–25 . In our study, only connective tissue disease, trauma, and surgery exhibited significantly higher incidence rates in the DVT group compared to the PE group.…”

“…Previous studies have suggested that chronic lung disease, chronic digestive disease, trauma, and tumors could induce pulmonary inflammation. [22][23][24][25] In our study, only connective tissue disease, trauma, and surgery exhibited significantly higher incidence rates in the DVT group compared to the PE group. Nevertheless, this difference does not provide an explanation for the higher rate of pneumonia lesions observed in the PE group, which could potentially be attributed to PE.…”

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

“…For lung samples, serial 4 μm-thick sections of the left lung were collected. Another subset of mice were euthanised by rapid decapitation following sodium pentobarbitone overdose, for collection of bronchoalveolar lavage fluid (BALF) via in situ lung lavage [ 45 ]. Mice were then decapitated, and the brains extracted from the skull.…”

“…Digital lung slides were viewed with Aperio ImageScope v.12.4.3 at 10x magnification. Alveolar airspace size was quantified using the mean linear intercept (MLI) method [ 45 , 49 ]. Briefly, 20 equal length lines were drawn over images of H&E-stained lung cross-sections, then the number of intercepts with alveolar walls were counted.…”

Reply to Li et al.

“…Consequently, this dual impact may play a role in initiating or exacerbating susceptibility to COPD. There are indications that patients with inflammatory bowel disease (IBD) have an increased susceptibility to pulmonary manifestations ( 2 ), and animal studies have suggested that intestinal and systemic inflammation in colitis models would predispose these patients to lung pathologies ( 3 , 4 ). Moreover, a disturbed gut microbiota was observed after cigarette smoke and particulate matter exposure ( 5 – 7 ).…”