The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease

Abstract

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-α 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-α, 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 (FcγR- 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.

Keywords::

• biological therapy
• granulocytes
• inflammatory bowel disease
• leukocytapheresis
• lymphocytes
• monocytes
• ulcerative colitis

Acknowledgements

This work was supported in part by grants-in-aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research and Creative Scientific Research from the Japan Ministry of Education, Culture, Sports, Science and Technology; the Japan Ministry of Health, Labor and Welfare; the Japan Medical Association; Foundation for Advancement of International Science; Yakult Bio-Science Foundation; Research Fund of Mitsukoshi Health and Welfare Foundation. The authors thank Dr AR Saniabadi for critically reading the manuscript.