MODULATION OF ENDOTHELIAL-CELL FUNCTION BY NORMAL POLYSPECIFIC HUMAN INTRAVENOUS IMMUNOGLOBULINS - A POSSIBLE MECHANISM OF ACTION IN VASCULAR DISEASES

Intravenous immunoglobulin (IVIg) is increasingly used in the treatmen t of autoimmune and inflammatory diseases, including vasculitides and Kawasaki disease. However, the outcome of IVIg interaction with endoth elial cells of the vascular bed is not clear as yet. We have investiga ted the effect of IVIg on the in vitro activation of human endothelial cells, as assessed by cell proliferation and reverse transcription-po lymerase chain reaction-detected expression of mRNA coding for adhesio n molecules (intercellular adhesion molecule-1 and vascular cellular a dhesion molecule-1), chemokines (monocyte chemoattractant protein-1, m acrophage colony-stimulating factor, and granulocyte-macrophage colony -stimulating factor), and proinflammatory cytokines (tumor necrosis fa ctor-alpha, interleukin-1 beta, and interleukin-6), Mg inhibited proli feration of endothelial cells in a time-dependent manner. This effect was dependent on both Fc and F(ab')(2) fragments of the immunoglobulin molecule and was fully reversible. Tumor necrosis factor-alpha and in terleukln-1 beta also inhibited thymidine incorporation, but to a less er degree. IVIg had no effect on basal levels of mRNA coding for the a dhesion molecules, chemokines, and proinflammatory cytokines, IVIg ful ly down-regulated the expression induced by tumor necrosis factor-alph a or interleukin-1 beta of mRNA coding for these molecules. Thus, bloc kade of cellular proliferation and of cytokine-induced expression of a dhesion molecules, chemokines, and cytokines may explain the therapeut ic effect of IVIg in vascular and inflammatory disorders.