Tumor Necrosis Factor Alfa Antagonists for Pediatric Immune-Mediated Diseases

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2007;13(8):1-4. 

In This Article

Mechanism of Action

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine produced by T lymphocytes and macrophages. Its primary role in healthy individuals is to control infection by intracellular pathogens. In patients with immune-mediated diseases, TNFα levels are consistently elevated, leading to an abnormal sustained inflammatory response. The TNFα antagonists are monoclonal antibodies that bind to TNFα, forming a complex which inhibits its ability to bind to cell surface TNF receptors. Blocking TNFα activity prevents induction of proinflammatory cytokines, including interleukins (IL-1 and IL-6), as well as inhibiting expression of adhesion molecules responsible for leukocyte migration, activation of neutrophil and eosinophil functional activity, and induction of acute phase reactants.[2,3,4,5,6,7,8]

Infliximab is a chimeric monoclonal antibody, with a mouse variable region and a human constant region, that binds both soluble and transmembrane TNFα receptors. It does not bind TNFβ. Etanercept is a fully human, soluble fusion protein. It is formed from the linkage of two ligand-bearing regions of the p75 TNF receptor and the Fc portion of human IgG1. It binds both TNFα (soluble form only) and TNFβ. Adalimumab is a fully human monoclonal antibody to TNFα, produced by recombinant DNA technology. It does not bind to TNFβ.[3,4,5]

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