IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis.
- Author:
Su Jin HWANG
1
;
Doo Hyun CHUNG
Author Information
- Publication Type:Original Article
- Keywords: IL-4; knockout mice; cytokines; inflammation; lung
- MeSH: Alveolitis, Extrinsic Allergic; Animals; Bronchoalveolar Lavage Fluid; Chemokine CCL3; Chemokine CCL5; Chemokines; Cytokines; Hypersensitivity; Inflammation; Inhalation; Interleukin-4; Lung; Lung Diseases; Mice; Mice, Knockout; Neutrophils; Saccharopolyspora; T-Lymphocytes; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
- From:Immune Network 2008;8(3):90-97
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. METHODS: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. RESULTS: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-gamma, TGF-beta and TNF-alpha in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1alpha, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-gamma-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. CONCLUSION: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.
