IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization.
Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10-/-) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.
Mäkelä
M J
MJ
Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Kanehiro
A
A
Borish
L
L
Dakhama
A
A
Loader
J
J
Joetham
A
A
Xing
Z
Z
Jordana
M
M
Larsen
G L
GL
Gelfand
E W
EW
D000336:Aerosols; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D004558:Electric Stimulation; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005816:Genetic Complementation Test; D015316:Genetic Therapy; D007114:Immunization; D007249:Inflammation / Q000503:physiopathology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015289:Leukotrienes / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000503:physiopathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010544:Peroxidases / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012260:Ribonucleases; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000503:physiopathology
D000336:Aerosols; D001798:Blood Proteins; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D015289:Leukotrienes; D016210:Methacholine Chloride; D016753:Interleukin-10; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D012260:Ribonucleases