Effect of Genetic Variation of IL-13 on Airway Remodeling in Bronchial Asthma

• Published in: Allergology International Vol. 60; no. 3; pp. 291 - 298
• Main Authors: Nagashima, Hiromi, Nakamura, Yutaka, Kanno, Hiroyuki, Sawai, Takashi, Inoue, Hiroshi, Yamauchi, Kohei
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 2011; JAPANESE SOCIETY OF ALLERGOLOGY; Elsevier
• Subjects: Adult; Aged; Airway Remodeling - genetics; Asthma - genetics; Asthma - immunology; Asthma - pathology; bronchial asthma; bronchial biopsy; bronchial lavage fluid; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; Female; Fibroblasts - metabolism; Gene Expression Profiling; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; IL-13; Inflammation Mediators - metabolism; Interleukin-13 - genetics; Male; Middle Aged; polymorphisms; Respiratory Mucosa - pathology; bronchial asthma; bronchial lavage fluid; IL-13; polymorphisms; bronchial biopsy
• ISSN: 1323-8930; 1440-1592; 1440-1592
• DOI: 10.2332/allergolint.10-OA-0259

IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13Q110 is the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 110 of IL-13, and as we already know, individuals homozygous for glutamine (Q110/Q110) are strongly associated with asthma and IgE. IL13Q110 has been demonstrated to show that increased allergic inflammation depended on the enhanced IL-13-mediated Th2 effector function. Therefore, we investigated whether Q110/Q110 accelerated the decline in pulmonary function and development of airway remodeling of asthmatic patients in the general population. A total 336 asthmatic subjects living in Japan were recruited, genotyped, and had a pulmonary function test performed on them. To analyze airway inflammation and remodeling, bronchial lavage fluid (BLF) and endobronchial biopsy specimens were examined. Forced expiratory volume in one second (FEV1), %predicted, forced expiratory volume/forced vital capacity ratio, and forced expiratory flow 25-75%, % predicted were significantly decreased in Q110/Q110 compared to R110/R110, and the decline in FEV1 was increased significantly in Q110/Q110 compared to R 110/R110. The concentration of IL-13, IL-23, IL-11, GM-CSF, hyaluronic acid, and CCL8 in BLF were increased in Q110/Q110 compared to R110/R110 and the thickness of the subepithelial layer was thicker. Our study demonstrates that Q110/Q110 increases, at least in part, allergic inflammation and the propensity for airway remodeling, thus resulting in low lung function.