| First Author | Huaux F | Year | 2003 |
| Journal | J Immunol | Volume | 170 |
| Issue | 4 | Pages | 2083-92 |
| PubMed ID | 12574379 | Mgi Jnum | J:126708 |
| Mgi Id | MGI:3761897 | Doi | 10.4049/jimmunol.170.4.2083 |
| Citation | Huaux F, et al. (2003) Dual roles of IL-4 in lung injury and fibrosis. J Immunol 170(4):2083-92 |
| abstractText | Increased lung IL-4 expression in pulmonary fibrosis suggests a potential pathogenetic role for this cytokine. To dissect this role, bleomycin-induced pulmonary inflammation and fibrosis were analyzed and compared in wild type (IL-4(+/+)) vs IL-4-deficient (IL-4(-/-)) mice. Lethal pulmonary injury after bleomycin treatment was higher in IL-4(-/-) vs IL-4(+/+) mice. By administration of anti-CD3 Abs, we demonstrated that this early response was linked to the marked T lymphocyte lung infiltration and to the overproduction of the proinflammatory mediators such as TNF-alpha, IFN-gamma, and NO in IL-4(-/-) mice. In contrast to this early anti-inflammatory/immunosuppressive role, during later stages of fibrosis, IL-4 played a profibrotic role since IL-4(-/-) mice developed significantly less pulmonary fibrosis relative to IL-4(+/+) mice. However, IL-4 failed to directly stimulate proliferation, alpha-smooth muscle actin, and type I collagen expression in lung fibroblasts isolated from the wild-type mice. Upon appropriate stimulation with other known fibrogenic cytokines, fibroblasts from IL-4(-/-) mice were relatively deficient in the studied parameters in comparison to fibroblasts isolated from IL-4(+/+) mice. Taken together, these data suggest dual effects of IL-4 in this model of lung fibrosis: 1) limiting early recruitment of T lymphocytes, and 2) stimulation of fibrosis chronically. |
