Objectives: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is highly effective for the treatment of Crohn’s disease (CD) and rheumatoid arthritis (RA). Our experiments focused on RA and CD patients receiving infliximab. Since cytokine production is largely determined by genetic factors, the promoter polymorphisms of TNF-α were examined among these patients. Additionally, the changes caused by infliximab in the TNF-α-producing ability and apoptosis of peripheral blood mononuclear cells (PBMCs) were investigated. Methods: The TNF-α genotypes were analyzed by PCR-RFLP. The in vitro TNF-α production of the PBMCs was detected by flow cytometric analysis. The TNF-α concentration in the supernatant was measured by bioassay. Apoptosis was detected by annexin V-fluorescein isothiocyanate labeling. Results and Conclusions: 8 of the 12 nonresponder patients carried the TNF A allele associated with high TNF-α production. We suggest that the determination of TNF polymorphism may help identify more suitable candidates for infliximab treatment. Although in vitro infliximab treatment for 48 h resulted in significant (44.2 ± 1.17%) apoptosis in PBMCs, in ex vivo samples from RA patients who received infliximab, apoptosis was only 13.3 ± 1.6%. Furthermore, infliximab did not result in irreversible inhibition of the TNF-α-producing ability or in the significant apoptosis of PBMCs.

Keywords:
Tumor necrosis factor-α, Gene polymorphism, Infliximab, Apoptosis, Intracellular cytokine, Rheumatoid arthritis, Crohn’s disease
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© 2004 S. Karger AG, Basel
2004
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