title: Anticytokine therapy for osteoarthritis.
abstract: Osteoarthritis (OA) is a joint disease that involves degeneration of articular cartilage, weakening of the subchondral bone and limited intra-articular inflammation manifested by synovitis. Since the pathogenesis of OA involves multiple aetiologies, including mechanical, biochemical and genetic factors, it has been difficult to identify unique targets for therapy. Current pharmacological interventions focus primarily on improving symptoms. The rationale for the use of anticytokine therapy in OA is based on evidence from studies in vitro and in vivo that interleukin-1 (IL-1) and tumour necrosis factor (TNF)-alpha are the predominant pro-inflammatory and catabolic cytokines involved in the initiation and progression of articular cartilage destruction. Since the increased levels of catabolic enzymes, prostaglandins, nitric oxide (NO) and other markers in OA fluids and tissues appear to be related to elevated levels of IL-1 and TNF-alpha, therapies that interfere with the expression or actions of these cytokines are most promising. Other cytokines that are anti-inflammatory and are often detected, paradoxically, in OA tissues are also potential therapeutic agents for counteracting the cartilage destruction in OA. Identification of methods for early diagnosis is of key importance, since therapeutic interventions aimed at blocking or reversing structural damage will be more effective when there is the possibility of preserving normal homeostasis. At later stages, cartilage tissue engineering with or without gene therapy will also require anticytokine therapy to block damage to newly repaired cartilage. This review will focus on experimental approaches currently under study that may lead to elucidation of effective strategies for therapy in OA, with special emphasis on anticytokine therapy.
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115-5713, USA. mgoldrin@bidmc.harvard.edu
authors.forename: M B
authors.initials: MB
authors.lastname: Goldring
mesh_terms: D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines