Abstract
Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.
Publication types
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Clinical Trial
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute-Phase Proteins / antagonists & inhibitors
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Acute-Phase Proteins / biosynthesis*
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use*
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Antirheumatic Agents / pharmacology
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Antirheumatic Agents / therapeutic use
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / therapy
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Cytokines / antagonists & inhibitors*
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Cytokines / biosynthesis*
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Double-Blind Method
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Humans
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Infliximab
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / blood
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / blood
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Longitudinal Studies
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / blood
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Sialoglycoproteins / blood
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Solubility
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / immunology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Acute-Phase Proteins
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Antibodies, Monoclonal
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Antirheumatic Agents
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Cytokines
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IL1RN protein, human
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Interleukin-6
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Receptors, Tumor Necrosis Factor
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Sialoglycoproteins
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Tumor Necrosis Factor-alpha
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Infliximab