title: Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review.
abstract: Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians' complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the above mentioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.
authors.affiliation: Clinic for Orthopaedic Surgery Lovran, School of Medicine, University of Rijeka, Lovran, Croatia.
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Jotanovic
authors.forename: Radovan
authors.initials: R
authors.lastname: Mihelic
authors.forename: Branko
authors.initials: B
authors.lastname: Sestan
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Dembic
mesh_terms: D000368:Aged; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D007375:Interleukin-1; D017472:Receptors, Interleukin-1