Role of IL-17 in asthma pathogenesis and its implications for the clinic

Abstract

Introduction: Asthma is a respiratory disorder typically characterized by T-helper type 2 (Th2) inflammation that is mediated by cytokines, including IL-4, IL-5, and IL-13. Pathophysiologically, airway inflammation involving prominent eosinophilia, elevated IgE synthesis, airway hyperresponsiveness, mucus hypersecretion, and airway remodeling manifest clinically in patients as wheezing, breathlessness, chest tightness and episodic coughing. However, the Th2 paradigm falls short in interpreting the full spectrum of asthma severity. Areas covered: Severe asthmatics represent a distinct phenotype with their mixed pattern of neutrophilic-eosinophilic infiltration and glucocorticoid insensitivity making them refractory to currently available therapies. Th17 cells and their signature cytokine, IL-17, have been implicated in the development of severe asthma. Here, we review the contribution of IL-17 in the pathological features of asthma, gathered from both human and animal studies published in Pubmed during the past 10 years, and briefly discuss the clinical implications of targeting IL-17 imbalance in asthmatic patients. Expert opinion: With advancement in our understanding of the role of IL-17 in asthma pathology, it is clear that IL-17 is a targetable pathway which may lead to improvement in clinical symptoms of asthma. However, further elucidation of the complex interactions unfurled by IL-17 is essential in the empirical development of effective therapeutic options for refractory asthmatics.

Keywords: Airway remodeling; IL-17; Th17 cells; neutrophilic inflammation; severe asthma; steroid resistance.