Th17 can regulate silica-induced lung inflammation through an IL-1β-dependent mechanism.
Bottom Line: The Th17 response, which is induced by IL-1β, has been reported very important in chronic human lung inflammatory diseases.Treatment with an IL-1 type I receptor (IL-1RI) antagonist anakinra substantially decreased silica-induced lung inflammation and the Th17 response.Silica may induce IL-1β production from alveolar macrophages and promote inflammation by initiating a Th17 response via an IL-1β/IL-1RI-dependent mechanism.
Affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China; Department of Clinical Immunology, Dalian Medical University, Dalian, China.Show MeSH
Related in: MedlinePlus
Mentions: To assess the function of the IL-17/Th17 response in the inflammatory stage of silicosis, we examined the lung response to IL-17 neutralization. An anti-IL-17 mAb effectively neutralized IL-17 in the lung on days 1 and 4, significantly at day 4 (P < 0.05; Fig. 4A). Th17 cells in the spleen were decreased significantly in the anti-IL-17 mAb+silica group compared with Th17 cells in the control Ab+silica group (P < 0.05; Fig. 4B). These results demonstrated neutralization of IL-17 in mice treated with an anti-IL-17 mAb. Silica-induced lung inflammation was limited in the group administered anti-IL-17 mAb compared with mice administered control Ab (Fig. 4C). We then examined the accumulation of inflammatory cells (i.e., total cells, neutrophils, lymphocytes and macrophages) in BALF. Neutralization of IL-17 downregulated the total cell numbers in BALF significantly on days 1 and 4 (P < 0.05; Fig. 5A). Neutrophils in the anti-IL-17 mAb + silica group decreased significantly compared with those in the saline + silica group on days 1 and 4 (P < 0.05; Fig. 5B). Lymphocytes and macrophages in the anti-IL-17 mAb+silica group both decreased to varying degrees (Fig. 5C and D). These results support key functions for IL-17/Th17 in the development of lung inflammation in silicosis.
Affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China; Department of Clinical Immunology, Dalian Medical University, Dalian, China.