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

Abstract

All biological agents currently used for reducing TNFalpha 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-1beta monoclonal antibodies, the IL-1 Trap, IL-1 receptor type I antibodies, antibodies to the IL-1 receptor accessory chain and inhibitors of IL-1beta-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-1beta 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.