The Role of Cytokines in the Symbiotic Relationship between Leukocytes and Vascular Endothelia

Abstract

Inflammatory reactions and immunity involve close interactions between immunocompetent cells and the vessel wall (Baldwin, 1982). The extravasation and localization at inflammatory sites of leukocytes involve adhesion to and passage through endothelial linings. Changes in the vessel wall, including vasodilation and proliferation of capillary endothelial cells are well documented at sites of cell-mediated immune reactions involving leukocyte recruitment. In recent years, we and others have accumulated evidence indicating that inflammatory lymphokines released by leukocytes play a pivotal role in the interaction between vascular cells and circulating white blood cells. Soluble products released by lymphocytes and macrophages are potent regulators of various functions of vascular cells, such as proliferation, migration, production of colony stimulating factors and expression of class II (Ia) histocompatibility antigens. The molecules which mediate the symbiotic relationship of leukocytes with vascular cells have been, to some extent, defined recently. Thus interferon-γ (IFN-γ) has been shown to regulate the expression of Ia antigens in various cells including vascular endothelium (Pober et al., 1983). More recently, the mononuclear phagocyte products interleukin-1 (IL-1) and tumor necrosis factor (TNF) have been shown to profoundly affect the functional competence of vessel wall cells. IL-1 and TNF are released by mononuclear phagocytes following activation, and these monokines are likely to play a crucial role in various pathological conditions, including inflammatory reactions and endotoxin shock (for review Dinarello, 1985; Old, 1985).