Pathogenesis of Giant Cell Arteritis
Early in disease, following an unknown trigger, lymphocytic inflammation is confined to the adventitia and external elastic lamina. In the adventitia, dendritic cells are activated to produce chemokines which attract more dendritic cells, lymphocytes, and macrophages to the area. The activated dendritic cells process and present antigen resulting in T-cell activation. Dendritic cells produce interleukin (IL)-12 and IL-18 which promote Th-1 differentiation, whereas IL-1, IL-6, and IL-21 promote Th-17 differentiation. The activated Th1 cells secrete interferon-γ, which is important in macrophage activation and granuloma formation, whereas Th17 cells produce IL-17, which is a potent proinflammatory cytokine with multiple cellular effects leading to vascular inflammation and production of matrix metalloproteinases that destroy the internal elastic lamina. Growth and angiogenic factors (vascular endothelial growth factor) support the further influx of T cells and macrophages to the area. Closer to the lumen, neovascularization and macrophage-produced cytokines (platelet-derived growth factor, IL-1) cause prominent intimal proliferation that leads to ischemia.
