Multisystem interactions in the pathogenesis of vasculitis

The vasculitides are often considered diseases caused by an immune response to a causative antigen. However, multiple decision points are involved in guiding an inflammatory process toward healing and repair versus destruction and disease. This review focuses on determinants that have the potential to alter decision points but have only recently begun to attract attention. Vasculitic disorders often exhibit a strict age preference. Progress has been made in the understanding of immunosenescence and its implications for immunocompetence as well as for the development of chronic inflammation. A second aspect in the pathogenesis of vasculitis is the distinct tissue tropism, involving preference for vessels of defined sizes and distributions. Studies in giant cell vasculitis have begun to shed light on the interaction between the affected tissue and the inflammatory cells and suggest that the vascular microanatomy determines the organization of the infiltrate. An important role may be attributed to the tunica adventitia, which harbors regulatory cells and probably provides the port of entrance for infiltrating cells. Finally, data are accumulating on the importance of the host's immunoresponsiveness in the decision between a beneficial and a pathologic inflammation. Studies in giant cell arteritis have shown that differences in the immunomodulatory milieu that are partially accomplished through the action of cytokines are responsible for disease heterogeneity and outcome.