title: Soluble CD163, a specific macrophage activation marker, is decreased by anti-TNF-α antibody treatment in active inflammatory bowel disease.
abstract: Activated macrophages shed the haemoglobin-haptoglobin scavenger receptor CD163 into the circulation as soluble(s)-CD163. We measured sCD163 as an in vivo macrophage activation marker in patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving antitumour necrosis factor (TNF)-α antibody or prednisolone treatment. We also investigated the CD163 expression on circulating monocytes. 58 patients with CD, 40 patients with UC and 90 healthy controls (HC) were included. All patients had active disease at inclusion and were followed for 6 weeks of anti-TNF-α antibody or prednisolone treatment. We measured plasma sCD163 levels at baseline, 1 day, 1 week and 6 weeks after initiating treatment. CD163 expression on circulating CD14(+) monocytes was measured in 21 patients with CD receiving anti-TNF-α antibody treatment. Baseline sCD163 levels were elevated in patients with CD [1.99 (1.80-2.18) mg/l] and in patients with UC [2.07 (1.82-2.32) mg/l] compared with HC [1.51 (1.38-1.63) mg/l] (P < 0.001). Anti-TNF-α antibody treatment induced a rapid decrease in sCD163 levels in patients with CD and in patients with UC 1 day after treatment initiation (P < 0.05). One week of prednisolone treatment did not induce a reduction in sCD163 levels. Anti-TNF-α treatment normalized sCD163 levels in patients with UC, whereas patients with CD exhibited sustained increased sCD163 levels. In patients with CD, CD163 expression on CD14(+) monocytes was increased compared with HC. This study highlights that active CD and UC are associated with increased macrophage activation, as indicated by elevated sCD163 levels and monocytic CD163 expression. Anti-TNF-α antibody treatment induced a rapid decrease in sCD163 levels, suggesting a specific effect on macrophage activation in inflammatory bowel diseases.
authors.affiliation: Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C, Denmark; Department of Medicine, Horsens Regional Hospital, Horsens C, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Dige
authors.forename: S
authors.initials: S
authors.lastname: Støy
authors.forename: K L
authors.initials: KL
authors.lastname: Thomsen
authors.forename: C L
authors.initials: CL
authors.lastname: Hvas
authors.forename: J
authors.initials: J
authors.lastname: Agnholt
authors.forename: J F
authors.initials: JF
authors.lastname: Dahlerup
authors.forename: H J
authors.initials: HJ
authors.lastname: Møller
authors.forename: H
authors.initials: H
authors.lastname: Grønbaek
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood* / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000098902:CD163 Antigen
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha