Type 2 immune response associated with silicosis is not instrumental in the development of the disease.

It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4(-/-) mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor alpha (IL-4Ralpha), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG(1)) in the lungs of IL-4(-/-) and IL-4Ralpha(-/-) mice did not affect the development of the disease. Measurement of IL-13alpha2 receptor expression and IgG(2a), IL-12p70, and IFN-gamma levels in silica-treated IL-4(-/-) and IL-4Ralpha(-/-) animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.