title: Rifaximin for preventing acute graft-versus-host disease: impact on plasma markers of inflammation and T-cell activation.
abstract: In murine allogeneic hematopoietic cell transplantation models, inhibiting bacterial translocation stemming from conditioning-induced damage to the gut mucosa abrogates inflammatory stimulation of donor T cells, preventing acute graft-versus-host disease (AGVHD). We conducted a phase I trial to begin testing the hypothesis that rifaximin, a broadly acting oral antibiotic, would reduce systemic inflammation and T-cell activation. We administered rifaximin to 20 adolescents and younger adults (day -10 through day +30) receiving intensive conditioning. We measured the plasma level of interleukin-6, as a marker of conditioning-induced inflammation, and the levels of soluble tumor necrosis factor receptor-1 and soluble interleukin-2 receptor, as surrogate markers of AGVHD. We formed a historical control group (n=24), from a previous study of biomarkers in AGVHD. The increase in the treatment group's mean interleukin-6 level from baseline to day 0 was 73% less than that in the control group (P=0.006). The increase from baseline to day 15 in the treatment group's mean soluble tumor necrosis factor-1 and soluble interleukin-2 receptor levels was similar to the control group. Incidences of grade 2 to 4 AGVHD also did not differ. This suggests that rifaximin may abrogate bacterial translocation and resultant inflammation, but in alternative donor transplants this does not prevent downstream activation of donor T cells.
authors.affiliation: Aflac Cancer and Blood Disorders Center, Atlanta, GA 30322, USA. muna.qayed@choa.org
authors.forename: Muna
authors.initials: M
authors.lastname: Qayed
authors.forename: Amelia
authors.initials: A
authors.lastname: Langston
authors.forename: Kuang-Yueh
authors.initials: KY
authors.lastname: Chiang
authors.forename: Keith
authors.initials: K
authors.lastname: August
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hilinski
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Cole
authors.forename: Andre
authors.initials: A
authors.lastname: Rogatko
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
authors.forename: John T
authors.initials: JT
authors.lastname: Horan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy / Q000601:surgery*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D015375:Receptors, Interleukin-2 / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D019172:Transplantation Conditioning; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D012294:Rifamycins; D000078262:Rifaximin