Scientific corner

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile

Tomotaka Tanaka

Cureus 2023 Nov 16;15(11):e48913. doi: 10.7759/cureus.48913. eCollection 2023 Nov.

The major phenotypes of inflammatory bowel disease (IBD) include ulcerative colitis (UC) and Crohn’s disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBD myeloid lineage leukocytes are elevated with activation behavior and release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresis carriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatment have not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBD potentially may increase the risk of severe viral infection, non-drug granulomonocytapheresis should be a favorable treatment strategy. Further, by targeting granulomonocytapheresis to patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PubMed (nih.gov)

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PMC (nih.gov)

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.

https://pubmed.ncbi.nlm.nih.gov/23465691/

Scientific corner

Production of Interleukin-10 by combining a granulocyte and monocyte adsorption carrier with ulinastatin.

Shoichi Nishise 1Takeshi SatoYu SasakiKo NaginoDaisuke IwanoTakao YaoitaKazuya YoshizawaYuko NishiseHiroaki Takeda, Ther Apher Dial. 2012 Oct;16(5):449-55.

Interleukin (IL)-10 is an anti-inflammatory cytokine mainly produced by monocytes and is essential for the induction of anti-inflammatory intestinal macrophages with macrophage colony-stimulating factor (M-CSF). Thus, IL-10- and M-CSF-rich conditions in colonic tissues seem to contribute to the improvement of pathological conditions in patients with inflammatory bowel diseases (IBD). We have already reported that ulinastatin, a serine protease inhibitor, increases M-CSF production during granulocyte/monocyte (GM) adsorption to cellulose acetate (CA) beads (carriers for Adacolumn therapy). However, the effects of ulinastatin on IL-10 production have not been clarified. The aim of the present study was to clarify the effects of ulinastatin on IL-10 production during GM adsorption by in vitro experiments. Peripheral blood was divided into four groups: (Control) no ulinastatin added, no contact with CA beads; (1) no ulinastatin added, contact with CA beads; (2) ulinastatin added, no contact with CA beads; and (3) ulinastatin added, contact with CA beads. After incubation, IL-10 in the plasma was measured. Compared with the level in the Control group, plasma IL-10 was significantly higher only in group 3, in which ulinastatin was added in the presence of CA beads, but did not increase in the absence of CA beads. These results suggest that ulinastatin synergistically increases IL-10 production with monocyte adsorption stimuli. By increasing not only M-CSF but also IL-10, a combination of ulinastatin and Adacolumn therapy may improve clinical efficacy for the treatment of IBD in terms of the induction of anti-inflammatory intestinal macrophages.

https://pubmed.ncbi.nlm.nih.gov/23046370/

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