%0 Journal Article
%T Th17-Associated Cytokines as a Therapeutic Target for Steroid-Insensitive Asthma
%A Yuko Morishima
%A Satoshi Ano
%A Yukio Ishii
%A Shigeo Ohtsuka
%A Masashi Matsuyama
%A Mio Kawaguchi
%A Nobuyuki Hizawa
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/609395
%X Steroid-insensitive asthma is an infrequent but problematic airway disease that presents with persistent symptoms, airflow limitation, or recurrent exacerbations even when treated with steroid-based therapies. Because of unsatisfactory results obtained from currently available therapies for steroid-insensitive asthma, a better understanding of its pathogenesis and the development of new targeted molecular therapies are warranted. Recent studies indicated that levels of interleukin (IL)-17 are increased and both eosinophils and neutrophils infiltrate the airways of severe asthmatics. IL-17 is a proinflammatory cytokine mainly secreted from helper T (Th) 17 cells and is important for the induction of neutrophil recruitment and migration at sites of inflammation. This review focuses on the pathogenetic role of Th17 cells and their associated cytokines in steroid-insensitive asthma and discusses the prospects of novel therapeutic options targeting the Th17 signaling pathway. 1. Introduction Asthma is a very common disease that affects many people, men and women, young and old, worldwide. Although asthma is mostly well controlled by conventional therapies including inhaled corticosteroids, about 5¨C10% of asthma patients have a severe phenotype described as ¡°fatal or near-fatal asthma,¡± ¡°severe asthma,¡± ¡°steroid-dependent asthma,¡± ¡°steroid-insensitive asthma,¡± ¡°difficult to control asthma,¡± ¡°poorly controlled asthma,¡± ¡°brittle asthma,¡± or ¡°irreversible asthma¡± [1]. The causes of these conditions are complex and most likely heterogeneous. Some can be explained by insufficient or inadequate treatment, while others explained by airway inflammation that is resistant to conventional treatment. Continuous exposure to aggravating factors and/or associated comorbid conditions may exert a deleterious influence on asthma control, but a certain type of airway inflammation may also contribute to standard therapy unresponsiveness. As such, the pathogenesis of uncontrollable asthma, especially steroid-insensitive asthma, has been a long-standing interest among researchers attempting to establish a novel strategy for the treatment of patients with persistent symptoms, irreversible airflow obstruction, or frequent exacerbations even under adequate treatment. The current consensus on asthma is that the main underlying pathology is chronic airway inflammation in which inflammatory cells, such as eosinophils and helper T (Th) 2 lymphocytes, play a role. The Th1/Th2 paradigm has offered important insights into the pathogenesis of asthma, and there is no doubt that this classical
%U http://www.hindawi.com/journals/jir/2013/609395/