Immune Netw.  2008 Sep;8(3):90-97. 10.4110/in.2008.8.3.90.

IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis

• Hwang SJ
• Chung DH

• KMID: 2163198
• DOI: http://doi.org/10.4110/in.2008.8.3.90

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.

Keyword

IL-4; knockout mice; cytokines; inflammation; lung

MeSH Terms

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
Chemokine CCL3
Chemokine CCL5
Chemokines
Cytokines
Interleukin-4
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha