Different roles of interleukin-10 in onset and resolution of asthmatic responses in allergen-challenged mice.
OBJECTIVE
Although interleukin (IL)-10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL-10 in experimental asthma using ovalbumin (OVA)-sensitized mice.


METHODS
Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA-specific IL-10-producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti-IL-10 antibody on airway responsiveness and inflammation were also evaluated.


RESULTS
The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL-10-producing CD4+ T cells was observed, mainly in the CD45RB(low) subset, for several days after the OVA challenge. Anti-IL-10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti-IL-10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge.


CONCLUSIONS
Intrinsic IL-10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL-10 induces airway hyperresponsiveness, while in the late phase IL-10 contributes to the resolution of eosinophilic inflammation.
Matsumoto
Koichiro
K
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Inoue
Hiromasa
H
Tsuda
Miyuki
M
Honda
Yasuko
Y
Kibe
Atsuko
A
Machida
Kentaro
K
Yoshiura
Yuki
Y
Nakanishi
Yoichi
Y
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007114:Immunization; D016753:Interleukin-10 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D000485:Allergens; D000906:Antibodies; D015848:Interleukin-5; D016753:Interleukin-10; D010047:Ovalbumin