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Higher IL-6 Levels and Changes in TGF-β are Associated with Lung Impairment in Pulmonary Tuberculosis
Pulmonary tuberculosis (PTB) is associated with granuloma formation, necrosis and cavitation in lung tissue. Lung injury in PTB can persist despite microbiological cure and is associated with chronic obstructive pulmonary disease (COPD) independent of smoking exposure. Furthermore, pulmonary sequelae of PTB are an underrecognized cause of respiratory disability and excess mortality.
Our prior work in India found up to 50% of PTB cases had impaired lung function post-treatment. We also found a positive correlation between the duration of symptomatic illness prior to PTB treatment and severity of lung impairment posttreatment. These data suggest that acute lung injury in PTB likely occurs during the preor early-treatment period, and that lung tissue repair and remodeling during treatment may play an important role in post-PTB lung disease.
However, the pathogenesis of PTB-associated lung disease is unclear. Preclinical studies have suggested a pro-fibrotic role of interleukin (IL)1-β, IL-6, IL-4, IL-17 and transforming growth factor (TGF)-βs in the lungs[4, 5]; markers which also play an important role in the host immune response in PTB. Further, tumor necrosis factor alpha (TNF-α) and matrix metalloproteinases (MMPs) have been implicated in lung tissue destruction and cavitation in PTB.
There is growing interest in the utility of host directed therapies (HDTs); adjunctive therapies that modulate immune mechanisms in the host; for improving clinical outcomes. HDTs with anti-inflammatory properties could potentially prevent or limit the extent of lung injury in PTB. Therefore, we measured the association of potentially modifiable inflammatory markers implicated in lung tissue destruction and fibrosis, with respiratory morbidity and impaired lung function in a prospective cohort of adults with drug sensitive PTB.
Gupte AN, Selvaraju S, Gaikwad S, Mave V, Kumar P, Babu S, Andrade BB, Checkley W, Bollinger R, Gupta A. Higher IL-6 Levels and Changes in TGF-β are Associated with Lung Impairment in Pulmonary Tuberculosis. ERJ Open Research Jan 2020, 00390-2020; DOI: 10.1183/23120541.00390-2020