Scientific corner

The effect of granulocyte and monocyte adsorptive apheresis on serum cytokine levels in patients with ulcerative colitis

Yosuke Toya 1Toshimi ChibaTomomi MizutaniKunihiko SatoSatoshi KasugaiNozomi MatsudaShunsuke OrikasaSho ShibataYukito AbikoRisaburo AkasakaNaoki YokoyamaShuhei OanaShigeru HirotaMasaki EndoKazuyuki Suzuki, Cytokine. 2013 Apr;62(1):146-50.

Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn has been reported to be effective as induction therapy in ulcerative colitis (UC). However, the effects of GMA on serial changes in cytokine levels have not been well characterized. We therefore, investigated cytokine levels in UC patients before and after treatment with GMA. A total of 16 patients with active UC, 10 men, and six women, mean age, 42.6 years were included. Fourteen patients had total colitis and two patients had left-sided colitis. The study included nine patients with a chronic intermittent course, six with a chronic continuous course and one with a single episode. The duration of each GMA session was 60 min at a flow rate of 30 mL/min as per study protocol. Serum levels of 17 cytokines were determined simultaneously using a Bio-Plex suspension array system before and after treatment with GMA. Serum interleukin (IL)-10 and macrophage inflammatory protein-1β levels were increased significantly in UC patients after GMA treatment compared to pre-treatment levels (P < 0.05). In particular, GMA treatment caused a significant increase in serum IL-10 levels compared to pre-treatment in patients with total colitis or with a chronic intermittent UC course. In conclusion, this investigation showed that GMA was associated with a marked increase in serum level of the anti-inflammatory cytokine, IL-10. The rise in circulating IL-10 is interesting, and potentially a significant factor in the efficacy of GMA in patients with inflammatory bowel diseases.

Scientific corner

Immunoregulatory Effects of Adsorptive Granulocyte and Monocyte Apheresis in Patients with Drug Refractory Crohn’s Disease

Kazuko Nagase 1Ken FukunagaShinichiro KashiwamuraTomoaki KonoKoji KamikozuruYoko YokoyamaNobuyuki HidaYoshio OhdaNaohisa TakedaKoji YoshidaMasaki IimuroRisa KikuyamaKyoichi KatoHiroto MiwaTakayuki Matsumoto, Ther Apher Dial. 2011 Aug;15(4):367-73.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn’s disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-β1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-β1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.

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