Rheumatology Advance Access published online on February 28, 2003
Rheumatology, doi:10.1093/rheumatology/keg171
Rheumatology © British Society for Rheumatology 2003; all rights reserved
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Original Papers
1 Department of Immunology, Allergology and Rheumatology, University of Antwerp, Belgium
* Corresponding author. E-mail: wim.stevens{at}ua.ac.be.
Received 18 December 2001
; accepted 18 October 2002
Introduction. It has been shown that T lymphocytes and monocytes/macrophages, producing pro-inflammatory cytokines, play a pivotal role in the pathophysiology of rheumatoid arthritis (RA). In recent placebo-controlled double-blind randomized studies, chimeric (human/mouse) tumour necrosis factor- Objective. To investigate whether anti-TNF Methods. An intracellular flow cytometric technique was applied to measure interleukin 1 Results. Basal levels and production (after 8 h) of IL-1 Conclusion. Anti-TNF
Key words: Tumour necrosis factor-Influence of therapy with chimeric monoclonal tumour necrosis factor-
antibodies on intracellular cytokine profiles of T lymphocytes and monocytes in rheumatoid arthritis patients
(TNF) antibodies (cA2) proved to be very effective in improving clinical disease activity and reducing inflammatory parameters in RA. therapy influences the in vitro intracellular cytokine production in peripheral blood monocytes and T lymphocytes of RA patients after one single (24 h) and multiple intravenous infusions (6 months).
(IL-1), IL-6, TNF, IL-10 and IL-12 in monocytes and IL-2, IL-4 and interferon-
in T lymphocytes of 15 patients, before, after 24 h and after 6 months of therapy with monoclonal chimeric anti-TNF antibodies (3 mg/kg, bimonthly i.v.). All patients were on stable therapy with methotrexate (15-20 mg/week i.m.). Cytokine content in monocytes was measured directly after blood sampling (basal levels), after 8 h of culture (spontaneous production) and after 8 h of stimulation with lipopolysaccharides (LPS-stimulated production)., IL-6 and TNF were significantly decreased 24 h after the first administration of anti-TNF (for IL-1 P < 0.01; for IL-6 P < 0.01; for TNF P < 0.003) and after 6 months of therapy (for IL-1 P < 0.02; for IL-6 P < 0.03; for TNF P < 0.001). For IL-12, basal levels were significantly decreased 24 h and 6 months after the start of therapy with anti-TNF antibodies (P=0.0001; P=0.003, respectively). In contrast, IL-10 production increased significantly after 24 h and after 6 months (P=0.02; P=0.01). The TH2/TH1 cytokine ratio in CD4+ T cells was significantly increased after 24 h and after 6 months of anti-TNF therapy (P=0.003; P=0.0007). therapy might down-regulate the monocytic capacity to produce pro-inflammatory cytokines and induces a shift to a more pronounced anti-inflammatory TH2 cytokine production., Anti-TNF therapy, RA, Cytokine.
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