title: Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.
abstract: BACKGROUND
  Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy.
  
  
  METHODS
  Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7-10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR).
  
  
  RESULTS
  Apoptosis resistance of T and B lymphocytes was observed only in steroid-refractory and -dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)-10 was markedly increased at baseline in steroid-responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response).
  
  
  CONCLUSIONS
  Apoptosis resistance of mucosal T and B cells in steroid-refractory and -dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL-10 at an early stage of active steroid-sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid-dependent and -refractory CD patients share similar molecular and cellular pathophysiological mechanisms.
authors.affiliation: Department of Gastroenterology, Hospital Universitari Mútua de Terrassa, University of Barcelona, Research Foundation Mútua de Terrassa, Terrassa, Barcelona, Catalonia, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Santaolalla
authors.forename: Josep
authors.initials: J
authors.lastname: Mañé
authors.forename: Elisabet
authors.initials: E
authors.lastname: Pedrosa
authors.forename: Violeta
authors.initials: V
authors.lastname: Lorén
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Bañares
authors.forename: Josefa
authors.initials: J
authors.lastname: Mallolas
authors.forename: Anna
authors.initials: A
authors.lastname: Carrasco
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.forename: Mercè
authors.initials: M
authors.lastname: Rosinach
authors.forename: Montserrat
authors.initials: M
authors.lastname: Forné
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Espinós
authors.forename: Carme
authors.initials: C
authors.lastname: Loras
authors.forename: Michael
authors.initials: M
authors.lastname: Donovan
authors.forename: Pere
authors.initials: P
authors.lastname: Puig
authors.forename: Miriam
authors.initials: M
authors.lastname: Mañosa
authors.forename: Miquel A
authors.initials: MA
authors.lastname: Gassull
authors.forename: Josep M
authors.initials: JM
authors.lastname: Viver
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D047468:Immunoprecipitation; D016753:Interleukin-10 / Q000172:deficiency*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D016753:Interleukin-10