Apoptosis resistance of mucosal lymphocytes and IL‐10 deficiency in patients with steroid‐refractory Crohn's disease

Apoptosis resistance of mucosal lymphocytes and IL‐10 deficiency in patients with steroid‐refractory Crohn's disease

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/antii...

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Bibliographic Details
Published in:Inflammatory bowel diseases Vol. 17; no. 7; pp. 1490 - 1500
Main Authors: Santaolalla, Rebeca, Mañé, Josep, Pedrosa, Elisabet, Lorén, Violeta, Fernández‐Bañares, Fernando, Mallolas, Josefa, Carrasco, Anna, Salas, Antonio, Rosinach, Mercè, Forné, Montserrat, Espinós, Jorge C., Loras, Carme, Donovan, Michael, Puig, Pere, Mañosa, Miriam, Gassull, Miquel A., Viver, Josep M., Esteve, Maria
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-07-2011
Subjects:
Adrenal Cortex Hormones - pharmacology
Adult
Apoptosis
Biopsy
Blotting, Western
Case-Control Studies
Corticoids
Crohn Disease - metabolism
Crohn Disease - pathology
Crohn's disease
Cytokines
Drug Resistance
Enzyme-Linked Immunosorbent Assay
Evolution
Female
Flow Cytometry
Fluorescent Antibody Technique
Follow-Up Studies
Humans
IL‐10
Immunoenzyme Techniques
Immunofluorescence
Immunohistochemistry
Immunophenotyping
Immunoprecipitation
Inflammatory bowel diseases
Interleukin 10
Interleukin-10 - deficiency
Intestine
Leukocytes (mononuclear)
lymphocyte apoptosis resistance
Lymphocytes - immunology
Lymphocytes - metabolism
Lymphocytes B
Lymphocytes T
Macrophages
Male
Middle Aged
Mucosa
Mucous Membrane - immunology
Mucous Membrane - metabolism
Plasma cells
Polymerase chain reaction
Prognosis
Prospective Studies
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Steroid hormones
steroid resistance
Survival Rate
Therapeutic applications
Ulcerative colitis
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Summary: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. (Inflamm Bowel Dis 2010;)
Bibliography:Supported by La Marató de TV3 Foundation; ref 03/1810 Ferring International; GETECCU‐Otsuka; and the Spanish Ministry of Science and Innovation. BFU 200764887.
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ISSN:1078-0998
1536-4844
1536-4844
DOI:10.1002/ibd.21507