The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases.
Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment of nine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.
Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
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Blandizzi
IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
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Gionchetti
IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
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Armuzzi
Chair and Division of Rheumatology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
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Caporali
Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
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Chimenti
Department of Paediatrics, Rheumatology Unit, Anna Meyer Childrens Hospital, University of Florence, Firenze, Italy.
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Cimaz
Ocular Immunology Unit, Ophthalmology, Unit, Arcispedale S Maria Nuova Reggio, Reggio, Emilia, Italy.
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Cimino
Rheumatology Unit, Interdisciplinary Department of Medicine, Medical School, University of Bari, Bari, Italy.
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Lapadula
Gastroenterology Unit, Anna Meyer Childrens Hospital, Department of Paediatrics, University of Florence, Firenze, Italy.
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Lionetti
G. Pini Orthopedic Institute, Milano, Italy.
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Marchesoni
CEIS  Economic Evaluation and HTA (EEHTA), IGF Department, University of Tor Vergata, Rome, Italy.
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Marcellusi
CEIS  Economic Evaluation and HTA (EEHTA), IGF Department, University of Tor Vergata, Rome, Italy.
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Mennini
Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
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Salvarani
Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy.
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Girolomoni
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha