Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma.
Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.
Wang
C-C
CC
Department of Pediatrics, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China.
Fu
C-L
CL
Yang
Y-H
YH
Lo
Y-C
YC
Wang
L-C
LC
Chuang
Y-H
YH
Chang
D-M
DM
Chiang
B-L
BL
D000256:Adenoviridae / Q000235:genetics*; D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D001980:Bronchi / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000032:analysis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000032:analysis / Q000235:genetics*; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D018418:Th2 Cells / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods
C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D053590:Interleukin 1 Receptor Antagonist Protein; D015848:Interleukin-5; D007371:Interferon-gamma; D010047:Ovalbumin