A Pilot Study of Centrifugal Leukocyte Apheresis for Corticosteroid-Resistant Active Ulcerative Colitis.

Abstract

Corticosteroids are effective in bringing about a clinical remission in patients with ulcerative colitis. However, in severely relapsed cases, corticosteroids are not always effective even whena high dosage is administered. In addition, the long-term use of corticosteroids often causes serious side effects. Therefore, an alternative treatment for active ulcerative colitis is necessary in order to avoid these clinical problems. In the present pilot study, the efficacy of leukocytapheresis using a centrifugal procedure was evaluated for corticosteroid-resistant, active ulcerative colitis. Fourteen patients with corticosteroid-resistant severely active ulcerative colitis were treated by leukocytapheresis.Thirteen patients (92.9 %) achieved clinical remission within 4 weeks after the apheresis, and remained in remission for 8 months on average without any additional corticosteroid therapy. In the remaining patient, in whomremission was not induced, a total colectomy was performed immediately after the fourth course of leukocytapheresis. No significant side effects were noticed throughout the therapy. Both colonoscopic and histological examinations confirmed the beneficial effect of this procedure in terms of the reduction of severe inflammation of the affected colon. Wefound that the expression of two adhesion molecules, L-selectin and VLA4a, on the surface of peripheral leukocytes was decreased after this new therapy.

Why is leukocytapheresis effective in inflammatory bowel diseases?

“…2 By processing 3 l of peripheral blood, corresponding to half of the body's blood, it is assumed that most circulating activated leukocytes can be removed and replaced by the naïve leukocytes from bone marrow or marginal pools. This phenomenon is also confirmed by the decrease in activated T cells, 3 the leukocytes expressing adhesion molecules such as L-selectin and integrins, 4 and the reactive oxygen species (ROS) 5 after apheresis. Based on the relative selectivity of removed leukocytes, the Aducolumn removes granulocytes and monocytes preferentially and the Cellsorba (LCAP) and centrifugal leukocytapheresis removes granulocytes/monocytes and lymphocytes in equal amounts, indicating that clinical effects of each apheresis may be derived from different mechanisms in addition to the total removal of Reprint requests to: Y. Kohgo proinflammatory cytokines, there is a possibility that the decrease of proinflammatory cytokines IL-1 and TNFα and inflammatory cytokines IL-8 and RANTES are involved by apheresis as reported in patients with rheumatoid arthritis.…”

Therapeutic Efficacy of Leukocytapheresis in a Pregnant Woman with Severe Active Ulcerative Colitis

“…Leukocytapheresis has recently been used to induce remission in UC patients who fail to respond to corticosteroids [2,3,4,5,6,7,8]. Mechanisms by which leukocytapheresis induces clinical remission still are unknown.…”

“…In addition, some reports suggest that leukocytapheresis is associated with the remedial action on the cytokine network in a diseased state, returning it to a normal level via the inhibition of several proinflammatory cytokines and by enhancing production of inhibitory cytokines such as IL-4 and IL-10 [10, 11]. Three methods of leukocytapheresis have been used: centrifugation [3, 5, 8], filtration [2, 6], and passage through granulocyte and monocyte removal column [4, 7, 8]. A multicenter study of leukocytapheresis by centrifugation showed clinical improvement in 74% of 50 UC patients [5].…”

“…However, cyclosporine should be avoided if possible, since experience with this drug in pregnant women with UC, though limited to a few cases, suggests an apparent high incidence of prematurity and low birth weight [1]. Leukocytapheresis has recently been used to induce remission in UC patients who failed to respond to corticosteroids [2,3,4,5,6,7,8]. This report is the first description of the management of severe active UC in a pregnant woman by leukocytapheresis.…”

Current concept of pathophysiological understanding and natural course of ulcerative colitis

“…However, UC cannot be considered to be a Th2-mediated disease without restriction, because production of the IL4 cytokine is diminished. The recognition of Tcells as being pivotal in the pathogenesis of UC has led to promising attempts to treat UC by removal of T-cells through therapeutic leukapheresis [44,45,46].…”