[Biological modulation of IL-1 activity: role and development of its natural inhibitor IL-1Ra].
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.
Dayer
J-M
JM
Hopital Cantonal, Divison d'Immunologie et d'Allergologie, Genève, Switzerland. Jean-Michel.Dayer@hcuge.ch
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012795:Sialoglycoproteins / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha