A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis-clinical efficacy and production of interleukin-1 receptor antagonist.

Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI < or = 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP. Copyright 2008 Wiley-Liss, Inc.