Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira), and certolizumab (Cimzia), are approved for treating inflammatory bowel disease (IBD), including Crohn's disease.
Infliximab, adalimumab, and golimumab belong to the IgG1 subclass, while certolizumab is a recombinant antibody with a Fab fragment conjugated to PEG. These antibodies work by binding to and neutralizing both soluble and membrane-bound TNF, preventing its binding to receptors and mitigating the inflammatory response in Crohn's disease. They lead to symptomatic improvement and remission. Infliximab is administered intravenously, while adalimumab, golimumab, and certolizumab are given subcutaneously. Adverse effects of these anti-TNF therapies include infusion reactions, respiratory infections, reactivation of latent tuberculosis, and the development of antibodies against the drugs.
Tumor necrosis factor, or TNF, a proinflammatory cytokine, exists in soluble or membrane-bound form.
TNF-receptor interaction triggers NF-κB, T-cell activation, and leukocyte infiltration, resulting in Crohn's disease-associated transmural inflammation, making TNF a prime therapeutic target.
Anti-TNF therapy employs IgG1 monoclonal antibodies like infliximab, adalimumab, and golimumab. Also, a recombinant antibody, certolizumab, lacking the Fc portion, features a Fab fragment conjugated to polyethylene glycol.
Infliximab is administered via intravenous infusions, whereas the others are usually given subcutaneously.
They bind to TNF and block TNF-receptor interaction, inhibiting inflammatory cellular responses.
In addition, their Fc portion promotes antibody-mediated apoptosis of activated immune cells, effectively curbing inflammation.
Notably, they cause serious infections like bacterial sepsis, tuberculosis, and hepatitis B reactivation.
Additionally, infusion reactions such as fever, headache, and chest pain may also occur.
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