Influence of Plasma Exchange on Serum Levels of Cytokines and Adhesion Molecules in ANCA-Positive Renal Vasculitis

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Abstract
Background: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. Methods: Serum levels of IL-1β, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener’s granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. Results: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1β and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. Conclusion: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.