AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the periphera...AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.展开更多
AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be succe...AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.展开更多
文摘AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.
文摘AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.
