LNTERLEUKIN-1 (IL-1), A CYTOKINE PRODUCED BY CHONDROCYTES AND OTHER CELLS IN THE JOINT, PLAYS AN IMPORTANT ROLE IN CARTILAGE DEGRADATION. IL-1 STIMULATES PROSTAGLANDIN E2, NITRIC OXIDE, AND MATRIX METALLOPROTEASES, WHICH PROMOTE JOINT DEGRADATION. IN ADDITION, IL-1 SUPPRESSES JOINT REPAIR BY INHIBITING COLLAGEN SYNTHESIS. FURTHERMORE, IL-1 IS AN ENDOGENOUS PYROGEN, WHICH REGULATES THE IMMUNE SYSTEM SYSTEMICALLY AND LOCALLY IN ACUTE AND CHRONIC DISEASE, AUGMENTS ACTIVATION OF T AND B LYMPHOCYTES, CAUSES MACROPHAGES TO RELEASE PROTEOLYTIC ENZYMES AND CHEMOTACTIC FACTORS, AND ALSO STIMULATES OSTEOCLASTS TO RESORB BONE.
A UNIDIRECTIONAL IL-1-DRIVEN CYTOKINE CASCADE DISTURBS THE HOMEOSTASIS OF THE EXTRACELLULAR MATRIX OF ARTICULAR CARTILAGE IN OA LEADING TO CARTILAGE DAMAGE AT A PACE FASTER THAN THE PACE OF REPAIR.
DIACEREIN EXERTS ITS PHARMACOLOGIC ACTION THROUGH ITS ACTIVE METABOLITE - RHEIN.
* INHIBITS INTERLEUKIN-1 ACTIVITY, THE MAIN CYTOKINE INVOLVED IN CARTILAGE DESTRUCTION CONSEQUENTLY, REDUCING COLLAGENASE PRODUCTION IN ARTICULAR CARTILAGE.
* DOSE-DEPENDENTLY INHIBITS SUPEROXIDE ANION PRODUCTION, CHEMOTAXIS AND PHAGOCYTIC ACTIVITY OF NEUTROPHILS, AND MACROPHAGE MIGRATION AND PHAGOCYTOSIS, THEREBY REDUCING ARTICULAR CARTILAGE DAMAGE. THROUGH THIS UNIQUE PHARMACOLOGICAL ACTIVITY DIACEREIN HAS DEMONSTRATED ANTI-INFLAMMATORY EFFECTS AND PROTECTION AGAINST THE DEVELOPMENT OF OSTEOARTHRITIS IN WELL-KNOWN ANIMAL MODELS.