IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation.
Interleukin-10 was originally described as a factor that inhibits cytokine production by murine Th1 clones. Recent studies have since shown that IL-10 can also downregulate Th2 clones and their production of IL-4 and IL-5. Because of its immuno-suppressive properties, IL-10 has been suggested as a potential therapy for allergic inflammation and asthma. However, the pathophysiological role of IL-10 in vivo has not been clearly elucidated. We investigated the effects of IL-10 administration on the production of IgE, cytokine and allergen-induced Th2 cytokine production as well as its effects on eosinophilic inflammation. We established GATA-3/TCR double transgenic (GATA-3/TCR-Tg) mice by crossing GATA-3 transgenic mice with ovalbumin (OVA)-specific TCR transgenic mice; these mice were then sensitized using an intraperitoneal injection of OVA adsorbed to alum and challenged with the intratracheal instillation of an allergen. When GATA-3/TCR-Tg mice sensitized with OVA and alum were injected with C57-IL-10 cells before OVA inhalation, the levels of IL-5, IL-13, and IL-4 decreased by 40-85% and number of eosinophils decreased by 70% (P<0.03) in the murine bronchoalveolar lavage fluid (BALF). These results suggest that IL-10 plays an important role downstream of the inflammatory cascade in the Th2 response to antigens and in the development of BALF eosinophilia and cytokine production in a murine model of asthma. These immunosuppressive properties in animal models indicate that IL-10 could be a potential clinical therapy for the treatment of allergic inflammation.
Department of Microbiology, Kitasato University Allied Health Science, Sagamihara, Kanagawa, Japan.
Shinichiro
S
Kosaka
Hidekazu
H
Tamauchi
Masazumi
M
Terashima
Hiroko
H
Maruyama
Sonoko
S
Habu
Hidero
H
Kitasato
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology*; D050990:GATA3 Transcription Factor / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000485:Allergens; D016207:Cytokines; D050990:GATA3 Transcription Factor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin