Role of IL-6 in asthma and other inflammatory pulmonary diseases

Abstract

The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality. Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease. Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected. IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung. However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD. IL-6 may therefore be a germane target for treatment of these and other chronic lung disease. Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases.

Keywords: IL-6; chronic lung diseases.

Figure 1

Potential mechanisms by which IL-6 can contribute to lung diseases. IL-6 in the lung can be produced by different sources such as epithelial cells, interstitial fibroblasts, macrophages and other inflammatory cells. The production is induced in response to a variety of stimuli, defined as “insults” because they often cause cell stress or damage. These include allergens, respiratory viruses, excercice, environmental particles, inhaled toxic particles. IL-6 can regulate different aspects of the CD4 T cell mediated response including cytokine production, sIL-6R production, suppressive activity. These mediators in turn contribute to the damage of the lung through their effects on mucus production, matrix deposition, protease release from granulocytes among others. In the presence of sIL-6R, IL-6 can also regulate different functional aspects of non-immune cells such as epithelial cells.