Yujin Nishioka ¹, Goh Murayama ¹, Makio Kusaoi ¹, Daichi Takemasa ², Kenta Kaneda ², Taiga Kuga ¹, Yukitomo Hagiwara ¹, Takumi Saito ¹, Yu Yamaji ¹, Yoshifumi Suzuki ³, Tetsutaro Nagaoka ³, Ken Yamaji ¹, Naoto Tamura ¹

Ther Apher Dial. 2024 Nov 20. doi: 10.1111/1744-9987.14234. Online ahead of print.

Introduction: Granulocyte/monocyte adsorption therapy can manage mild-to-moderate inflammatory bowel disease by removing activated granulocytes and monocytes. We evaluated granulocyte/monocyte adsorption using new columns with reduced bead size and theoretically enhanced adsorption.

Methods: We assessed granulocyte/monocyte adsorption in rats with colitis by analyzing cell changes and cytokine production.

Results: Granulocyte/monocyte adsorption with the new columns improved histology in rats with colitis. Contrary to expectations, the adsorption rate of granulocytes/monocytes into the blood did not show a significant improvement. However, flow cytometry showed increased B cells in peripheral blood mononuclear cells and newly formed B cells in the bone marrow, which produced more interleukin-10 than peripheral blood B cells. Newly formed B cells adoptively transferred into colitis rats accumulated at the inflammation site and tended to inhibit intestinal shortening.

Conclusions: Newly formed B cells with strong interleukin-10 production may alleviate inflammation. The new columns suggest potential for controlling colitis.

Tomoyuki Nakamura, Kazuhiro Moriyama, Toshikazu Sakai, Yu Kato & Osamu Nishida 

Ren Replace Ther 10, 51 (2024). https://doi.org/10.1186/s41100-024-00565-9

Background

Sepsis 3 definitions have shifted the focus from nonspecific inflammation to sepsis as an organ dysfunction caused by a dysregulated host response to infection. Neutrophils have become therapeutic targets because of their intimate but complex involvement in sepsis. We conducted ex vivo and animal experiments to apply a granulocyte and monocyte adsorption column, which is clinically used for inflammatory bowel disease, in sepsis. In this study, the biocompatibility was evaluated in sepsis-like hypercytokinemia.

Methods

Six female outbred pigs were anesthetized. Extracorporeal direct hemoperfusion (DHP) with an Adacolumn or a sham column was initiated after lipopolysaccharide (LPS) administration. The DHP was performed for 2 h at a blood flow rate (QB) of 30 or 60 mL/min. Blood samples were collected before and during the DHP (30, 60, 90, and 120 min). The percentage change in white blood cell count, platelet count, and cytokine concentration was compared between the Adacolumn and sham columns.

Results

The percentage change in white blood cells were 96 (95–98)% and 106 (101–108)% in the Adacolumn and sham groups, respectively, at QB = 60 mL/min (p < 0.01). The percentage change in platelets were 95 (90–96)% and 97 (93–99)% in the in the Adacolumn and sham groups, respectively, at QB = 60 mL/min (not significant; n.s.). At QB = 60 mL/min, the percentage change in tumor necrosis factor-α, interleukin (IL)-6, and IL-10 were 92 (81–106)%, 95 (93–102)%, and 98 (95–100)%, respectively, for the Adacolumn and 100 (95–102)%, 98 (87–104)%, and 97 (93–99)%, respectively, for the sham column. The percentage change in white blood cell counts, platelet counts, and all cytokines at QB = 30 and 60 mL/min showed similar trends.

Conclusion

The biocompatibility of the Adacolumn was evaluated using a porcine LPS-induced inflammation model. No decrease in platelet counts or significant cytokine production was observed, suggesting that the Adacolumn could be safely used in patients with sepsis with QB = 30–60 mL/min for 2 h. However, production of mediators other than cytokines remains unknown and requires further investigation.

Jiménez-Cortegana Carlos , Palomares Francisca , Alba Gonzalo, Santa-María Consuelo , de la Cruz-Merino Luis , Sánchez-Margalet Victor , López-Enríquez Soledad Frontiers in Immunology 14,2024, doi.org=10.3389/fimmu.2023.1321051

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the “yin-yang” role of DCs to improve the understand of this type of cells in disease progression.

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)

Yosuke Toya ¹, Toshimi Chiba, Tomomi Mizutani, Kunihiko Sato, Satoshi Kasugai, Nozomi Matsuda, Shunsuke Orikasa, Sho Shibata, Yukito Abiko, Risaburo Akasaka, Naoki Yokoyama, Shuhei Oana, Shigeru Hirota, Masaki Endo, Kazuyuki 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/

Shoichi Nishise ¹, Takeshi Sato, Yu Sasaki, Ko Nagino, Daisuke Iwano, Takao Yaoita, Kazuya Yoshizawa, Yuko Nishise, Hiroaki 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/