[Role of anti-TNF therapy in rheumatoid arthritis].
TUMOR NECROSIS FACTOR: TNF is a cytokine produced by several types of cells, but mainly by monocyte-macrophages, activated endothelial cells, fibroblasts, and joint cartilage chondrocytes. The circulating form of TNF alpha (homotrimere) is derived from its membrane form by cleavage induced by a metalloprotease called TACE. This cytokine plays a pivotal role in the inflammatory reaction in conjunction with IL-1 and IL-6. The effect of TNF alpha is mediated by two membrane receptors carried on the surface of target cells (TNF-RI p55 and TNF-RII p75) which are released into the biological fluids (synovial fluid and plasma). ARGUMENTS FOR A PATHOGENIC ROLE: Transgenic mice carrying the human gene for TNF alpha develop polyarthritis suggesting this cytokine is directly implicated in the pathogenesis. In diverse cell types in rheumatoid joints, TNF alpha and its receptors can be identified by immunohistochemistry techniques as can TNF alpha mRNA by RT-PCR.
Anti-TNF alpha antibodies can effectively attenuate or prevent arthritis in the main experimental models. TNF alpha can also be neutralized with soluble receptors, TNF alpha RI or TNF alpha RII. The efficacy of these two therapeutics has been proven in rheumatoid arthritis, but with a short-term though remnant effect, leading to iterative injections and/or combinations with methotrexate. Short-term side effects are mild but the long-term infectious and oncogenic adverse effects remain to be determined. Is this simply a powerful antiinflammatory treatment or a real curative treatment? A precise examination of radiographic scores will be required to provide the answer to this question.
Meyer
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Service de Rhumatologie, Hôpital Bichat, Paris. olivier.meyer@bch.ap-hop-paris.fr
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000627:therapeutic use; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010919:Placebos; D012333:RNA, Messenger / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012460:Sulfasalazine / Q000627:therapeutic use; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007166:Immunosuppressive Agents; D010919:Placebos; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C099374:Ro 45-2081; D012460:Sulfasalazine; D000069285:Infliximab; D000068800:Etanercept; D008727:Methotrexate