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Role of interleukin-10 in lung repair during influenza infection

University of British Columbia

The mammalian lung is intricately designed for effective gas exchange. However, infections such as influenza can damage the lung tissue and can cause a critical decrease in lung performance. Influenza is a single stranded RNA virus from the Orthomyxoviridae family. Seasonal influenza outbreaks cause up to 600 deaths in Canada each year, with increased death tolls during years with pandemic strains. Influenza A virus primarily infects the epithelial cells of the respiratory system and leads to acute respiratory infections. Tissue destruction occurs both as a result of viral-mediated apoptotic pathways, and as a consequence of the cytolytic immune response that is essential to bring the infection under control. The immune system attempts to minimize damage by producing key anti-inflammatory molecules, of which Interleukin-10 (IL-10) is a particularly potent example. IL-10 is a pleotropic cytokine that not only functions as an anti-inflammatory cytokine, but has been shown to have a role in immune stimulation, increase cytoskeletal repair and aid in the recovery of epithelial integrity. We hypothesized that IL-10 may have an effect on the remodeling and repair of lung epithelium during and after influenza A virus infection. We determined that IL-10 is up-regulated in response to infection. The timing of increased IL-10 also coincided with the height of damage, inflammation and onset of repair during an influenza infection. We used a human bronchial epithelial cell line (16HBE) to develop a model to assess if IL-10 had a direct effect on epithelial repair. Preliminary data suggested that IL-10 may inhibit epithelial cell proliferation, but further research is required. Our data suggest that IL-10 does not appear to have a role in direct epithelial proliferation but could still have a role in repair. A better understanding of the signals involved in epithelial cell repair could lead to the development of novel therapies that will minimize/mitigate lung damage caused by influenza, as well as other lung diseases.

Text

2016-09-02

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/59050

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/