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Modulation of Endothelial Cell Function by Normal Polyspecific Human Intravenous Immunoglobulins: A Possible Mechanism of Action in Vascular Diseases

https://doi.org/10.1016/S0002-9440(10)65670-2Get rights and content

Intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune and inflammatory diseases, including vasculitides and Kawasaki disease. However, the outcome of IVIg interaction with endothelial cells of the vascular bed is not clear as yet. We have investigated the effect of IVIg on thein vitro activation of human endothelial cells, as assessed by cell proliferation and reverse transcription-polymerase chain reaction-detected expression of mRNA coding for adhesion molecules (intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1), chemokines (monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor), and proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6). IVIg inhibited proliferation 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-α and interleukin-1β also inhibited thymidine incorporation, but to a lesser degree. IVIg had no effect on basal levels of mRNA coding for the adhesion molecules, chemokines, and proinflammatory cytokines. IVIg fully down-regulated the expression induced by tumor necrosis factor-α or interleukin-1β of mRNA coding for these molecules. Thus, blockade of cellular proliferation and of cytokine-induced expression of adhesion molecules, chemokines, and cytokines may explain the therapeutic effect of IVIg in vascular and inflammatory disorders.

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Supported in part by grant 97043 from Rhône-Poulenc Rorer (Paris, France) and the Central Laboratory of the Swiss Red Cross (Bern, Switzerland). CX was supported by 24-month fellowship no. 3Q4/044 from the French Foreign Ministry and the French Embassy in Beijing, China.

This work was presented in abstract form at the European Renal Association, European Dialysis and Transplant Association Annual Congress, Geneva, Switzerland, September 21–24, 1997, and at the American Society of Nephrology Meeting in San Antonio, TX, November 2–5, 1997.

CX's present address is Department of Histology and Embryology, Shanghai Second Medical University, Shanghai, China. NL's present address is Laboratory of Experimental Surgery, Department of Clinical Surgery, Federal University of Santa Catarina, Florianopolis, Brazil.

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