TNF-α inhibitors, such as etanercept and infliximab, downregulate cytokines which lead to inflammation. This is because TNF-α is the "master regulator" of the inflammatory (immune) response in many organ systems, and directs other cytokines to cause cell destruction and inflammation. Autoimmune diseases are caused by an overactive immune response.
TNF-α is an acute phase reactant released from macrophages. This causes fever and hypotension, and does so by leukocyte (lymphocyte) recruitment. Thus, TNF-α inhibitors block this pathway and decrease lymphocyte activation and migration.
Macrophages release TNF-α, which is used to induce and maintain granuloma formation. Inhibition of TNF-α causes granulomas to breakdown. This is not always helpful, as in diseases like TB, granuloma breakdown leads to disseminated disease.
TNF-α inhibitors are useful in treating IBD, such as Crohn's disease. This disease is characterized by noncaseating granulomas and lymphoid aggregates leading to transmural bowel wall inflammation.
Rheumatoid arthritis is an autoimmune disease which can be treated with TNF-α inhibitors. It is characterized by cytokine and type III and IV hypersensitivity mediated destruction of synovial joints.
Also known as juvenile idiopathic arthritis, is a seronegative, arthritis and inflammation of the synovium of joints, usually without a known cause. This is treated with newer TNF-α inhibiting drugs.
Psoriasis is a common skin autoimmune disorder characterized by silvery scaling plaques and papules, which typically develop on the knees and elbows. TNF-α inhibiting drugs are often used to treat this disorder.
Ankylosing spondylitis is a chronic inflammatory arthritis which is associated with "bamboo spine" on x-ray and HLA-B27 serum protein. It can be treated with this class of medications.
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