Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice.
This report examines the effect of recombinant murine (rm) IL-10 on antigen-induced cellular recruitment into the airways of sensitized Balb/c mice. The intranasal instillation of 10 micrograms ovalbumin induced an early (6-24 h) increase in the number of neutrophils, and a late rise (24-96 h) in that of eosinophils in the bronchoalveolar lavage (BAL) fluid and bronchial tissue. A single intranasal instillation of 0.01-0.1 microgram of rmIL-10, administered concurrently with ovalbumin, but not 1 or 3 h thereafter, dose-dependently inhibited both airway neutrophilia and eosinophilia. This phenomenon was suppressed by treating the sensitized mice with 1 mg/mouse of a neutralizing anti-IL-10 mAb, which increased significantly ovalbumin-induced neutrophil and eosinophil accumulation in the BAL fluid. These results suggest that antigen stimulation may trigger the in vivo generation of IL-10, which, in turn, participates in the leukocyte infiltration into the airways. rmIL-10 also reduced TNF-alpha release in the BAL fluid observed 1 and 3 h after antigen challenge. Furthermore, the intranasal instillation of an anti-TNF-alpha antiserum to sensitized mice markedly reduced ovalbumin-induced neutrophil and eosinophil accumulation in the BAL fluid. These findings indicate that leukocyte infiltration into the airways of antigen-challenged mice is regulated by IL-10. Furthermore, inhibition of TNF-alpha production by rmIL-10 suggests that allergic airway inflammation and TNF-alpha formation are parallel events in this model.
Zuany-Amorim
C
C
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/Institut National de la Santé et de la Recherche Médicale No. 285, Paris, France.
Hailé
S
S
Leduc
D
D
Dumarey
C
C
Huerre
M
M
Vargaftig
B B
BB
Pretolani
M
M
D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000276:immunology; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D006967:Hypersensitivity / Q000473:pathology / Q000503:physiopathology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000941:Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010047:Ovalbumin