Tumor Necrosis Factor alpha (TNF-alpha) is a multifunctional cytokine that mediates inflammation, immune regulation, and cellular proliferation. This cytokine is converted to its active form by TNF-alpha converting enzyme (TACE). Pathological increases in TNF-alpha activity have been associated with a wide variety of inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer. Inhibiting the conversion of TNF-alpha to its active form by inhibiting TACE represents a potential treatment for these diseases.

The current technology provides peptides, derived from an N-terminal fragment of the TACE protein, that inhibit TACE activity. Also described are methods of using these peptides to lower levels of active TNF-alpha. These peptides could be used as a treatment for TNF-alpha-mediated inflammatory diseases.