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Inflamm Bowel Dis ; 14(5): 591-6, 2008 May.
Article in English | MEDLINE | ID: mdl-18240280

ABSTRACT

BACKGROUND: Under experimental chronic inflammation, tumor necrosis factor (TNF)-alpha plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-alpha is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. METHODS: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. RESULTS: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients. CONCLUSIONS: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal/administration & dosage , B-Lymphocytes/immunology , Crohn Disease/immunology , Immunoglobulin M/immunology , Spleen/physiology , Adult , Crohn Disease/blood , Crohn Disease/drug therapy , Dose-Response Relationship, Drug , Female , Flow Cytometry , Follow-Up Studies , Humans , Infliximab , Male , Microscopy, Interference , Middle Aged , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors
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