title: Short-term intratracheal use of PEG-modified IL-2 and glucocorticoid persistently alleviates asthma in a mouse model.
abstract: Regulatory T (Treg) cells play an important role in allergic airway diseases, and upregulation of Treg cells is a potential therapeutic strategy for asthma. In this study, we show that short-term intratracheal use of IL-2 combined with glucocorticoid alleviates antigen-induced airway inflammation and reduces airway hyperresponsiveness by expanding antigen-nonspecific Treg cells, with a decrease in T helper 2 (Th2) cells and Th2-associated cytokines. We also designed a long-acting polyethylene glycol (PEG)-modified IL-2 and demonstrated that the optimal dosage form is IL-2(PEG) plus budesonide, which can upregulate Treg cells and ameliorate asthma at a lower dose. The therapeutic effect was faster than treatment with dexamethasone and was effective at a low dose suitable for humans that could last for at least 6 weeks. This study unveils a new therapeutic regimen and suggests that such endogenous Treg therapy could be a useful tool to persistently alleviate asthma.
authors.affiliation: Department of Hematology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Kefei
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Hematology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Jiexian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key laboratory of medical molecular virology, Institutes of biomedical sciences and institute of medical microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Weiya
authors.initials: W
authors.lastname: Bai
authors.affiliation: Key laboratory of medical molecular virology, Institutes of biomedical sciences and institute of medical microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Hematology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Xiamen Amoytop Biotech Co., Ltd, Xiamen 360000, People's Republic of China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key laboratory of medical molecular virology, Institutes of biomedical sciences and institute of medical microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Hematology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid; D019819:Budesonide / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014132:Trachea
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D011092:Polyethylene Glycols; D019819:Budesonide; D003907:Dexamethasone