title: ISU201 enhances the resolution of airway inflammation in a mouse model of an acute exacerbation of asthma.
abstract: Glucocorticoids are commonly used for treating asthma and its exacerbations but have well-recognised adverse effects and are not always effective. Few alternative treatments exist. Using a murine model of an acute exacerbation of asthma, we assessed the ability of ISU201, a novel protein drug, to suppress the inflammatory response when administered after induction of an exacerbation. Sensitised mice were chronically challenged with a low mass concentration of aerosolised ovalbumin, and then received a single moderate-level challenge to simulate an allergen-induced exacerbation. ISU201 was administered to mice 2 and 8 hours later, while pulmonary inflammation and expression of mRNA for chemokines and proinflammatory cytokines were assessed after 4, 12, and 24 hours. Relative to vehicle-treated controls, ISU201 suppressed accumulation of pulmonary neutrophils and eosinophils, while accelerating the decline in CXCL1, TNF-α, and IL-6 in lavage fluid and lung tissue. ISU201 significantly reduced peak expression of mRNA for the chemokines Cxcl9 and Cxcl10, the adhesion molecules Icam1 and Vcam1, and the proinflammatory cytokines Il1b, Il12p40, and Csf1. The ability of ISU201 to promote resolution of inflammation suggests that it may have potential as an alternative to glucocorticoids in the management of asthma, including when administered after the onset of an acute exacerbation.
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Garthwaite
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hsu
authors.affiliation: Isu Abxis Co., Ltd., 696-1 Sampyeong-dong, Bundang-ku, Seongnam 463-400, Republic of Korea.
authors.forename: Hyouna
authors.initials: H
authors.lastname: Yoo
authors.affiliation: Isu Abxis Co., Ltd., 696-1 Sampyeong-dong, Bundang-ku, Seongnam 463-400, Republic of Korea.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Park
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Geczy
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
authors.affiliation: Inflammation and Infection Research, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Cristan
authors.identifier: 0000-0002-0702-0210
authors.initials: C
authors.lastname: Herbert
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics; D054370:Chemokine CXCL9 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics
chemical_list: D015703:Antigens, CD; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C000604004:Csf1r protein, mouse; C587672:IL1B protein, mouse; C000592775:ISU201; C090509:Icam1 protein, mouse; D053583:Interleukin-1beta; D010446:Peptide Fragments; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018799:Intercellular Adhesion Molecule-1