Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation

• Published in: Current opinion in pharmacology 2004-08, Vol.4 (4), p.378-385
• Main Author: Dinarello, Charles A
• Format: Article
• Language: English
• Subjects: Animals; Humans; Inflammation - drug therapy; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - physiology; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1471-4892; 1471-4973
• DOI: 10.1016/j.coph.2004.03.010

All biological agents currently used for reducing TNFα activity in disease are neutralization strategies; however, there are several strategies for reducing interleukin (IL)-1 activities: the IL-1 receptor antagonist (IL-1Ra), anti-IL-1β monoclonal antibodies, the IL-1 Trap, IL-1 receptor type I antibodies, antibodies to the IL-1 receptor accessory chain and inhibitors of IL-1β-converting enzyme, now termed caspase-1. In fact, caspase-1 inhibitors are the first orally active agents that target cytokines, as these inhibitors prevent the processing and release of active forms for IL-1β and IL-18, which is a member of the IL-1 family. The IL-1 Trap is a new concept in using soluble forms of cytokine receptors to bind and neutralize a specific cytokine. The Trap takes advantage of the high affinity of the two signaling chains of the cell surface IL-1 receptor linked by the Fc portion of IgG1. The IL-1Ra is currently approved to treat rheumatoid arthritis; in over 75 000 patients, the IL-1Ra has provided insights into the role of IL-1 in local and systemic inflammation, as well as the safety of long-term reduction of IL-1 activity.