Giant-cell arteritis pathogenesis

Giant-cell arteritis (GCA) involves larges arteries, especially aorta and extra-cranial branches of external carotid. Histo-pathological lesions affect all the layers of the artery leading to a segmental and focal panarteritis with a polymorphic cell infiltrate including T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and an intimal hyperplasia. The pathophysiology of GCA is not fully understood. After dendritic cell activation in the adventitia, CD4 T cells are recruited in the arterial wall and polarized into Th1 and Th17 cells that produce IFN-gamma and IL-17. These cytokines activate macrophages, giant cells and smooth muscle cells inducing vascular remodeling leading to ischemic manifestations of GCA. Macrophages infiltrating the adventitia produce IL-1 beta and IL-6 that are responsible for general symptoms encountered in GCA. In this review, we discuss GCA pathogenesis, with emphasis on the role of IL-6 as a promising therapeutic target.