Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)alpha before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (IL)-1beta, IL-2, interferon (IFN)gamma, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.

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Low-CD25(High+)CD4(+), a subset of regulatory CD25(+)CD4(+) T cells and high-inflammatory CD28(-)CD4(+) T cells can exacerbate ulcerative colitis (UC). This study sought to investigate the frequency of CD25(High+)CD4(+) and CD28(-)CD4(+) T cells in patients with UC and the changes in these cells during Adacolumn granulocyte and monocyte adsorption apheresis (GMA). Subjects were 12 patients with active UC, 11 with quiescent UC, and 14 healthy volunteers (HVs). The mean clinical activity index was 15.7 +/- 2.2 in active UC and 4.5 +/- 1.1 in quiescent UC. Peripheral blood samples were stained with CD4, CD25, and CD28 antibodies for flow cytometry. Patients with active UC received GMA and blood samples were examined before and after the first GMA session. Patients with active UC (P < 0.04) or quiescent UC (P < 0.02) had a higher percentage of CD28(-)D4(+)T cells compared with HVs, while the percentage of CD28(+)CD4(+) T cells was lower in both UC groups compared with HVs (P = 0.03 and P < 0.02). Patients with active UC had a lower percentage of CD25(High+)CD4(+)T cells compared with quiescent UC patients (P < 0.001). A significant increase in CD25(High+)CD4(+) T cells was associated with GMA (P < 0.03). Low CD25(High+)CD4(+) and high CD28(-)CD4(+) are prominent features in UC. The increase in CD25(High+)CD4(+) T cells induced by GMA should contribute to improved immune function. Additional studies are warranted, since a low frequency of CD25(High+)CD4(+) (-) and a high frequency of CD28(-)CD4(+) (-) expressing T cells might be a predictor of clinical response to GMA.