Blockade of Interleukin-17 Restrains the Development of Acute Lung Injury

被引:47
作者
Li, Q. [1 ]
Gu, Y. [2 ]
Tu, Q. [3 ]
Wang, K. [3 ]
Gu, X. [3 ]
Ren, T. [3 ]
机构
[1] Tongji Univ, Sch Med, East Hosp, Dept Cardiothorac Surg, Shanghai 200092, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Dept Resp Med, Shanghai 200433, Peoples R China
[3] Tongji Univ, Sch Med, East Hosp, Dept Resp Med, 150 Jimo Rd,Pudong New Area, Shanghai 200120, Peoples R China
基金
中国国家自然科学基金;
关键词
RESPIRATORY-DISTRESS-SYNDROME; T-HELPER-CELLS; IL-17; CHEMOKINE; INFLAMMATION; LYMPHOCYTES; RECRUITMENT; VENTILATION; EXPRESSION; RELEASE;
D O I
10.1111/sji.12408
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Here, we explored the association between IL-17 and development of ALI using LPS-induced murine model. We found that IL-17 level was elevated in bronchoalveolar lavage (BAL) fluid of ALI mice. Upregulation of IL-17 resulted in increased severity of ALI as evidenced by decreased body weight and survival rate, elevated level of total protein and albumin in BAL fluid, as well as more apparent histopathology changes of lung. Induction of ALI was impaired in IL-17-deficient mice. Management of IL-17 could modulate LPS-induced pulmonary inflammation, as reflected by the total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Of note, blockade of IL-17 effectively inhibited the lung inflammation and alleviated ALI severity. Finally, we confirmed the clinical relevance and found that IL-17 expression was elevated and associated with the disease severity in patients with ARDS. In essence, IL-17 was crucial for development of ALI, suggesting a potential application for IL-17-based therapy in clinical practice.
引用
收藏
页码:203 / 211
页数:9
相关论文
共 39 条
[1]  
Albanesi C, 1999, J IMMUNOL, V162, P494
[2]   IL-17-producing T cells in lupus nephritis [J].
Apostolidis, S. A. ;
Crispin, J. C. ;
Tsokos, G. C. .
LUPUS, 2011, 20 (02) :120-124
[3]  
Crimi Ettore, 2004, Best Pract Res Clin Anaesthesiol, V18, P477, DOI 10.1016/j.bpa.2003.12.007
[4]   CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury [J].
D'Alessio, Franco R. ;
Tsushima, Kenji ;
Aggarwal, Neil R. ;
West, Erin E. ;
Willett, Matthew H. ;
Britos, Martin F. ;
Pipeling, Matthew R. ;
Brower, Roy G. ;
Tuder, Rubin M. ;
McDyer, John F. ;
King, Landon S. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (10) :2898-2913
[5]   Evolution of treatments for patients with acute lung injury [J].
Esper, AM ;
Martin, GS .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2005, 14 (05) :633-645
[6]   IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger [J].
Ferretti, S ;
Bonneau, O ;
Dubois, GR ;
Jones, CE ;
Trifilieff, A .
JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :2106-2112
[7]   Lung recruitment in patients with the acute respiratory distress syndrome [J].
Gattinoni, L ;
Caironi, P ;
Cressoni, M ;
Chiumello, D ;
Ranieri, VM ;
Quintel, M ;
Russo, S ;
Patroniti, N ;
Cornejo, R ;
Bugedo, G .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (17) :1775-1786
[8]   LY2439821, a Humanized Anti-Interleukin-17 Monoclonal Antibody, in the Treatment of Patients With Rheumatoid Arthritis A Phase I Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study [J].
Genovese, M. C. ;
Van den Bosch, F. ;
Roberson, S. A. ;
Bojin, S. ;
Biagini, I. M. ;
Ryan, Peter ;
Sloan-Lancaster, J. .
ARTHRITIS AND RHEUMATISM, 2010, 62 (04) :929-939
[9]   Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin [J].
Glader, P. ;
Smith, M. E. ;
Malmhall, C. ;
Balder, B. ;
Sjostrand, M. ;
Qvarfordt, I. ;
Linden, A. .
EUROPEAN RESPIRATORY JOURNAL, 2010, 36 (05) :1155-1164
[10]   Integrating acute lung injury and regulation of alveolar fluid clearance [J].
Guidot, David M. ;
Folkesson, Hans G. ;
Jain, Lucky ;
Sznajder, Jacob I. ;
Pittet, Jean-Francois ;
Matthay, Michael A. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2006, 291 (03) :L301-L306