Introduction of Infliximab

Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions. It is produced by a recombinant cell line cultured by continuous perfusion. Infliximab is an artificial antibody. It was originally developed in mice as a mouse antibody. Because humans have immune reactions to mouse proteins, the mouse common domains were replaced with similar human antibody domains. Infliximab was first approved by the FDA in 1998 as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder.

Mechanism of Action of Infliximab

Crohn's disease is a lifelong inflammatory disorder characterized by the presence of inflammatory ulcerative lesions in the gastrointestinal tract. Lesions most commonly involve the large and small bowel, giving rise to symptoms of abdominal pain, weight loss, gastrointestinal haemorrhage, and fistula formation. Lesions most commonly involve the large and small bowel, giving rise to symptoms of abdominal pain, weight loss, gastrointestinal haemorrhage, and fistula formation. To date, treatment has been geared towards symptomatic relief of disease exacerbations via pharmacological interventions such as aminosalicylates, corticosteroids, immunosuppressive agents, antibiotics, and nutritional therapy. Surgery is indicated in those patients who have failed to respond to medical management, or to correct intestinal obstruction or abscesses. Surgical intervention is by no means curative, with inflammatory episodes recurring in ⩾80% of patients after intestinal resection. The inflammatory response in Crohn's disease is regulated by intercellular mediators known as cytokines. The major contributing factor to chronic local inflammation in Crohn's disease is local mucosal overproduction of proinflammatory cytokines to anti-inflammatory cytokines. Tumour necrosis factor-α (TNF-α) is one of several proinflammatory mediators, which has a central role in chronic inflammatory conditions, such as Crohn's disease, rheumatoid arthritis, and other granulomatous diseases. Its hyperactivity and enhanced signaling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. Infliximab is a chimeric monoclonal antibody to TNF-α, developed as a therapeutic agent for TNF-α mediated diseases. Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNF-α and inhibits or prevents the effective binding of TNF-α with its receptors. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α, infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α.

Fig 1. Mechanism of Action of Infliximab

For research use only. Not intended for any clinical use.