The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are debilitating idiopathic inflammatory bowel diseases (IBDs) with symptoms that impair ability to function and quality of life. The aetiology of IBD is inadequately understood and, therefore, drug therapy has been empirical instead of based on sound understanding of the disease mechanisms. This has been a major factor for poor drug efficacy and treatment-related side effects that often add to disease complications. The development of biologicals, notably infliximab, to block TNF-alpha reflects some progress, but there is major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD by its very nature is exacerbated and perpetuated by inflammatory cytokines, including TNF-alpha, IL-6 and IL-12, for which activated peripheral blood lymphocytes, monocytes/macrophages and granulocytes are major sources. Hence, activated leukocytes should be appropriate targets of therapy. At present, three strategies are available for removing excess and activated leukocytes by leukocytapheresis: centrifugation, Adacolumn and Cellsorba. Centrifugation can deplete lymphocytes or total leukocytes, whereas Adacolumn selectively adsorbs granulocytes and monocytes together with a smaller fraction of lymphocytes (FcgammaR- and complement receptor-bearing leukocytes), and Cellsorba non-selectively removes all three major leukocyte populations. Efficacy has ranged from ‘none’ to an impressive 93% together with excellent safety profiles and downmodulation of inflammation factors. Furthermore, leukocytapheresis has shown strong drug-sparing effects and reduced the number of patients requiring colectomy or exposure to unsafe immunosuppressants, such as cyclosporin A. Leukocytapheresis removes from the body cells that contribute to IBD and, therefore, unlike drugs, it is not expected to induce dependency or refractoriness.
Developments in the apheresis procedure for the treatment of inflammatory bowel disease
Initially used to treat rheumatoid arthritis, nonselective therapeutic leukocytapheresis was applied to the treatment of inflammatory bowel disease (IBD) as early as the 1980s. Since then, the process has been further refined and 2 blood perfusion systems using membrane filtration are presently employed in Japan and Europe for the selective removal of leukocytes in patients with IBD: Cellsorba is a column of polyethylenephtarate fibers that captures lymphocytes and granulocytes, and Adacolumn is a column of cellulose acetate beads that selectively adsorb granulocytes and monocytes. These systems overcome the limitations of centrifugation. Leukocytapheresis has been shown to exert an overall anti-inflammatory effect, as peripheral leukocytes demonstrated a diminished capacity to produce inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, IL-6, IL-8, and IL-1beta. In addition, down-regulation in the expression of adhesion molecule L-selectin and a shift toward a more immature granulocyte phenotype were observed in the peripheral blood. The safety and beneficial therapeutic effect of leukocytapheresis in IBD are being investigated further.
Contact UsFor more informationContact Us