Anti-TNF-α therapies: The next generation

Michael A. Palladino, Frances Rena Bahjat, Emmanuel A. Theodorakis, Lyle L. Moldawer

Research output: Contribution to journalReview articlepeer-review

522 Scopus citations


The functioning of the immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of serious inflammatory diseases. In particular, enhanced tumour-necrosis factor-α (TNF-α) synthesis is associated with the development of rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Inhibiting TNF-α activities in these diseases has been remarkably successful. However, the current injectable protein therapies have associated risks and limitations. An oral, small molecule that regulates TNF-α biology could either replace the injectables or provide better disease control when used alone or in conjunction with existing therapies. In this review, we discuss briefly the present understanding of TNF-α-mediated biology and the current injectable therapies in clinical use, and focus on some of the new therapeutic approaches with oral, small-molecule inhibitors.

Original languageEnglish (US)
Pages (from-to)736-746
Number of pages11
JournalNature Reviews Drug Discovery
Issue number9
StatePublished - Sep 2003

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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