[Biological modulation of IL-1 activity: role and development of its natural inhibitor IL-1Ra]

Abstract

IL-1 and TNF-alpha are potent inducers of matrix metalloproteinases (MMP), eicosanoids, nitric oxide oxydase (iNOS), receptor activator of NF-kB ligand (RANKL), products involved in the destruction of the extracellular matrix, the cartilage and in bone resorption. IL-1, particularly important at the local level, is more potent than TNF-alpha in stimulating MMP and specifically in impeding cartilage repair. However, IL-1 and TNF-alpha strongly synergize in multiple biological functions. Blockade of IL-1 by IL-1 receptor antagonist (IL-1Ra, sIL-1RII) in combination with the soluble IL-1 accessory protein (IL-1R AcP) result in a long-term beneficial effect in chronic inflammatory diseases. The association with anti-TNF-alpha therapy may also represent a logical approach, considering the number of patients that do not respond to either compound alone.