Browse > Article
http://dx.doi.org/10.3904/kjim.2017.207

Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model  

Liang, Lin (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Hur, Jung (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Kang, Ji Young (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Rhee, Chin Kook (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Kim, Young Kyoon (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Lee, Sook Young (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Publication Information
The Korean journal of internal medicine / v.33, no.6, 2018 , pp. 1210-1223 More about this Journal
Abstract
Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.
Keywords
Asthma; Obesity; Anti-interleukin-7; Pravastatin; Inflammation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007;117:175-184.   DOI
2 Sumarac-Dumanovic M, Stevanovic D, Ljubic A, et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes (Lond) 2009;33:151-156.   DOI
3 Zuniga LA, Shen WJ, Joyce-Shaikh B, et al. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 2010;185:6947-6959.   DOI
4 Litonjua AA, Gold DR. Asthma and obesity: common early-life influences in the inception of disease. J Allergy Clin Immunol 2008;121:1075-1084.   DOI
5 Sood A, Ford ES, Camargo CA Jr. Association between leptin and asthma in adults. Thorax 2006;61:300-305.   DOI
6 Schachter LM, Salome CM, Peat JK, Woolcock AJ. Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness. Thorax 2001;56:4-8.   DOI
7 Bustos P, Amigo H, Oyarzun M, Rona RJ. Is there a causal relation between obesity and asthma? Evidence from Chile. Int J Obes (Lond) 2005;29:804-809.   DOI
8 Barlow JL, Flynn RJ, Ballantyne SJ, McKenzie AN. Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyperreactivity. Clin Exp Allergy 2011;41:1447-1455.   DOI
9 Schnyder-Candrian S, Togbe D, Couillin I, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 2006;203:2715-2725.   DOI
10 Jartti T, Saarikoski L, Jartti L, et al. Obesity, adipokines and asthma. Allergy 2009;64:770-777.   DOI
11 Jang AS, Kim TH, Park JS, et al. Association of serum leptin and adiponectin with obesity in asthmatics. J Asthma 2009;46:59-63.   DOI
12 Delgado J, Barranco P, Quirce S. Obesity and asthma. J Investig Allergol Clin Immunol 2008;18:420-425.
13 Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006;17:4-12.
14 Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ 2014;349:g5517.   DOI
15 Muc M, Mota-Pinto A, Padez C. Association between obesity and asthma: epidemiology, pathophysiology and clinical profile. Nutr Res Rev 2016;29:194-201.   DOI
16 King GG, Brown NJ, Diba C, et al. The effects of body weight on airway calibre. Eur Respir J 2005;25:896-901.   DOI
17 Calixto MC, Lintomen L, Schenka A, Saad MJ, Zanesco A, Antunes E. Obesity enhances eosinophilic inflammation in a murine model of allergic asthma. Br J Pharmacol 2010;159:617-625.   DOI
18 Baffi CW, Winnica DE, Holguin F. Asthma and obesity: mechanisms and clinical implications. Asthma Res Pract 2015;1:1.   DOI
19 Song C, Luo L, Lei Z, et al. IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma. J Immunol 2008;181:6117-6124.   DOI
20 Lintomen L, Calixto MC, Schenka A, Antunes E. Allergen-induced bone marrow eosinophilopoiesis and airways eosinophilic inflammation in leptin-deficient ob/ob mice. Obesity (Silver Spring) 2012;20:1959-1965.   DOI
21 Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18:716-725.   DOI
22 Endo Y, Yokote K, Nakayama T. The obesity-related pathology and Th17 cells. Cell Mol Life Sci 2017;74:1231-1245.   DOI
23 Leiria LO, Martins MA, Saad MJ. Obesity and asthma: beyond T(H)2 inflammation. Metabolism 2015;64:172-181.   DOI
24 Kim HY, Lee HJ, Chang YJ, et al. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med 2014;20:54-61.   DOI
25 Kudo M, Melton AC, Chen C, et al. IL-17A produced by ${\alpha}{\beta}$ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med 2012;18:547-554.   DOI
26 Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med 2010;104:1131-1137.   DOI
27 Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008;14:37-44.   DOI
28 Imamura M, Okunishi K, Ohtsu H, et al. Pravastatin attenuates allergic airway inflammation by suppressing antigen sensitisation, interleukin 17 production and antigen presentation in the lung. Thorax 2009;64:44-49.
29 Zhang X, Markovic-Plese S. Statins' immunomodulatory potential against Th17 cell-mediated autoimmune response. Immunol Res 2008;41:165-174.   DOI
30 Youssef S, Stuve O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002;420:78-84.   DOI
31 Celedon JC, Kolls JK. An innate link between obesity and asthma. Nat Med 2014;20:19-20.   DOI
32 Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 2014;222:R113-R127.   DOI
33 Zarkesh-Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJ. Leptin indirectly activates human neutrophils via induction of TNF-alpha. J Immunol 2004;172:1809-1814.   DOI
34 Kato H, Ueki S, Kamada R, et al. Leptin has a priming effect on eotaxin-induced human eosinophil chemotaxis. Int Arch Allergy Immunol 2011;155:335-344.   DOI
35 McLachlan CR, Poulton R, Car G, et al. Adiposity, asthma, and airway inflammation. J Allergy Clin Immunol 2007;119:634-639.   DOI
36 Lord G. Role of leptin in immunology. Nutr Rev 2002;60(10 Pt 2):S35-S38.
37 Holguin F, Bleecker ER, Busse WW, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol 2011;127:1486-1493.   DOI
38 Wu D, Molofsky AB, Liang HE, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011;332:243-247.   DOI
39 Ignacio RM, Kim CS, Kim SK. Immunological profiling of obesity. J Lifestyle Med 2014;4:1-7.   DOI
40 Brestoff JR, Kim BS, Saenz SA, et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 2015;519:242-246.   DOI