IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis
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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-γ, TGF-β and TNF-α in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1α, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-γ-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolarlavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administr ation 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.
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-γ, TGF-β and TNF-α in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1α, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-γ-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolarlavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administr ation 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.
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