Figure 1.

Pathogenetic actions of interleukin-8 (IL-8) and IL-17 on immune and stromal cells in multiple biological compartments in rheumatoid arthritis. (Left section) Schematic representation of the pathogenetic actions of IL-8 in the synovial tissue, blood vessel wall, and alveolar space in RA. Synovial tissue: The release of IL-8 by resident macrophages and fibroblast-like synoviocytes (FLS) plays a chemotactic action promoting the recruitment of immune cells toward the synovial tissue fueling tissue inflammation and promoting osteoclasts differentiation and activation leading to bone damage. Vessel wall: The release of IL-8 by infiltrating macrophages promotes the proliferation of smooth muscle cells and the activation of endothelial cells promoting plaque progression. Alveolar space: The release of IL-8 by alveolar macrophages enhances myeloid cell migration from circulation and promotes the development of hyper-fibrotic macrophages. Moreover, the release of IL-8 from mesenchymal cells induces their migration and proliferation in an autocrine loop. (Right section) Schematic representation of the pathogenetic actions of IL-17 in the synovial tissue, blood vessel wall, and alveolar space in RA. Synovial tissue: The release of IL-17 by Th17 lymphocytes promotes the activation of synovial macrophages and FLS contributing to the chronicity of synovitis. Moreover, IL-17 is a potent inducer of osteoclast/chondrocyte activation contributing to bone and cartilage damage. Vessel wall: The release of IL-17 by adaptive and innate immune cells promotes the chemotaxis of immune cells within the vessel plaque and promotes endothelial cell apoptosis, accelerating the atherosclerotic process and leading to increased cardiovascular risk. Alveolar space: The release of IL-17 interferes with the pneumocyte I autophagy process and its release by pneumocytes type II enhances fibroblast proliferation, which contributes to extracellular matrix deposition and lung fibrosis.