title: The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review.
abstract: Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid leucocytes such as the CD14(+) CD16(+) monocytes are major sources of tumour necrosis factor (TNF)-α, and therefore selective granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance efficacy of pharmacological therapy. However, studies in IBD have reported both impressive as well as disappointing efficacy outcomes, indicating that patients' demographic factors might determine responders or non-responders to GMA. Nonetheless, this non-drug intervention has an excellent safety profile, and therapeutic GMA is expected to expand. In this review, attempts have been made to compile an update on the mode of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than adsorption of excess neutrophils and TNF-producing CD14(+) CD16(+) monocytes per se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte growth factor and soluble TNF receptors, which are anti-inflammatory. Additionally, a sustained increase in lymphocytes including the regulatory CD4(+) CD25(+) T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the immune system is potentially very interesting in the context of treating immune-related diseases. Future studies are expected to add intriguing insights to the MoA of GMA.
authors.affiliation: Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, 26 Shirowacho, Hamamatsu, Japan. hanai@hamamatsu-minami.com
authors.forename: H
authors.initials: H
authors.lastname: Hanai
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Eberhardson
authors.forename: R
authors.initials: R
authors.lastname: Gruber
authors.forename: A R
authors.initials: AR
authors.lastname: Saniabadi
authors.forename: O
authors.initials: O
authors.lastname: Winqvist
authors.forename: R
authors.initials: R
authors.lastname: Lofberg
mesh_terms: D000327:Adsorption / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D017228:Hepatocyte Growth Factor / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000276:immunology; D007937:Leukapheresis / Q000379:methods*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor