The Role of Tumour Necrosis Factor in the Pathogenesis of Immune-Mediated Diseases

Abstract

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.

Evaluations of Audiovestibular Manifestations in Patients with Psoriasis

“…In the pathogenesis of immune mediated inflammatory diseases, TNF-α has been shown to play a critical role (18). Psoriasis, which responds well to TNF-α inhibitors in the treatment, also shows that TNF-α plays an important role in the aetiology of psoriasis.…”

Etanercept administration prevents the inflammatory response induced by carrageenan in the murine air pouch model

“…The development of TNF inhibitors in the last decade represented a great advance in the treatment of mild and severe forms of RA (Rosenblum and Amital 2011) and led to a better prognosis and clinical remission rate in patients with RA, especially those who are not well controlled with traditional disease-modifying anti-rheumatic drugs (DMARDs). The pivotal role of TNF in the pathogenesis and pathophysiology of RA has been documented by extensive preclinical and clinical investigations and confirmed by the efficacy of anti-TNF biotechnology-based drugs, such as etanercept, in the therapeutic management of several inflammatory diseases including RA (Blandizzi et al 2014).…”

Association of TNF-α gene promoter region polymorphisms in bovine leukemia virus (BLV)-infected cattle with different proviral loads

“…It is produced by many cell types, including monocytes/macrophages, T lymphocytes, neutrophils and NK cells. Its association with disease progression has been well established in several acute and chronic infections and autoimmune diseases in humans [3,6,19]. Overexpression of TNF-a in sheep experimentally infected with BLV might contribute to the progression of bovine leukosis in animals developing persistent lymphocytosis or B-cell lymphosarcoma [17,18].…”