Il-18 gene transfer by adenovirus prevents the development of and reverses established allergen-induced airway hyperreactivity.
We examined the role of IL-18 in preventing the development of and in reversing established allergen-induced airway inflammation and airway hyperreactivity (AHR), the cardinal features of asthma. IL-18, which potently induces IFN-gamma, was administered into the respiratory tract as cDNA in a replication-deficient adenovirus (Adv). Treatment of OVA-sensitized mice with the IL-18-expressing Adv reduced allergen-specific IL-4 production, airway eosinophilia, and mucus production, increased IFN-gamma production, and prevented the development of AHR. The effects of the IL-18 Adv treatment were dependent on the presence of IFN-gamma and IL-12. Moreover, administration of the IL-18 Adv to mice with established AHR greatly reduced AHR and IL-4 production and increased IFN-gamma production. These results demonstrate that IL-18, when administered by Adv into the respiratory tract, effectively reduces AHR and replaces an established Th2-biased immune response with a Th1-biased response.
Walter
D M
DM
Division of Immunology and Allergy, Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94305, USA.
Wong
C P
CP
DeKruyff
R H
RH
Berry
G J
GJ
Levy
S
S
Umetsu
D T
DT
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005822:Genetic Vectors / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology; D018664:Interleukin-12 / Q000276:immunology / Q000502:physiology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
D000485:Allergens; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin