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Keywords:

  • leucocytapheresis;
  • mode of action;
  • TNFα;
  • IL-1β;
  • bradykinin

Abstract

Adacolumn® is a medical device for adsorptive cytapheresis. It has been developed for selective adsorption of granulocytes and monocytes from peripheral blood of patients with immune disorders, such as autoimmune diseases and chronic inflammatory diseases. A double blind sham-controlled crossover study design was used in order to evaluate in vivo biological responses of leukocytes as well as biocompatibility during and after Adacolumn® cytapheresis in healthy volunteers. In addition, experiments were undertaken to further evaluate leukocyte reactions to Adacolumn® carrier (G-1: cellulose diacetate) beads in vitro. Six healthy volunteers, 4 males and 2 females, with a mean age of 26.7 years were randomly assigned to one of the two treatment arms in a crossover fashion. Three subjects received a single Adacolumn® treatment, followed by a single sham treatment at an interval of 7 days. The other three subjects received the two treatments in reverse order. All subjects were followed up 7 days after the last treatment. Additionally, in vitro investigations were carried out using blood from the healthy donors to examine the effect of G-1 beads on granulocyte functions. In vitro exposure of human peripheral blood to G-1 beads caused downregulation of L-selectin expression and upregulation of Mac-1 expression on granulocytes, leading to a marked reduction of adhesive capacity of granulocytes to endothelial cells. The exposure also led to decreased granulocyte chemotactic activity to IL-8. The number of granulocytes and monocytes clearly decreased during Adacolumn® cytapheresis. Granulocytes showed marked phenotypic changes of L-selectinLow and Mac-1Hi after passing through Adacolumn® in vivo. Expression of TNF-α and chemokine receptors was downregulated. In addition, TNF-α and IL-1β producing capacity of peripheral blood leukocytes was decreased after Adacolumn® cytapheresis and these changes lasted even one week after the cytapheresis. The level of complement fragments, C3a and C5a, increased, while bradykinin concentration did not change during Adacolumn® cytapheresis. Exposure of human peripheral blood to G-1 beads, both in vitro and in vivo, caused a significant reduction of adhesive capacity and proinflammatory cytokine producing capacity of peripheral blood leukocytes. Such changes were not observed after sham apheresis. Despite complement activation, tolerability of Adacolum® cytapheresis was not influenced. These findings may at least partly explain the beneficial effect of Adacolumn® cytapheresis in the treatment of autoimmune diseases. J. Clin. Apheresis © 2005 Wiley-Liss, Inc.