Osteoarthritis: can anti-cytokine therapy play a role in treatment?
- 1.1k Downloads
Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease’s progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in humans are still scarce. Although there is clear evidence that TNF-alpha plays a role in the pathophysiology of OA, only a few experimental trials have investigated the efficacy of blocking this pro-inflammatory cytokine in the treatment of OA. So far, the few studies available in humans using anti-TNF-alpha and IL-1 receptor antagonist are not remarkable, suggesting that further investigation and new therapeutic approaches are needed.
KeywordsIL-1 Inflammation Osteoarthritis TNF-alpha
- 1.Kramer JS, Yelin EH, Epstein WV (1983) Social and economic impacts of four musculoskeletal conditions: a study using national community-based data. J Rheumatol 26:901–907Google Scholar
- 2.Levy E, Ferme A, Perocheau D, Bono I (1993) Socioeconomic costs of osteoarthritis in France. Rev Rheum 60:63S–67SGoogle Scholar
- 9.Loeuille D, Chary-Valckenaere I, Champigneulle J, Rat AC, Toussaint F et al (2005) Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee. Correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum 52(11):3492–3501CrossRefPubMedGoogle Scholar
- 10.Bondeson J, Wainwright SD, Lauder S, Amos N et al (2006) The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Research & Therapy 8(6):1–12CrossRefGoogle Scholar
- 14.Goldring MB, Sandel LJ, Stephenson ML, Krane SM (1996) Immune interferon suppresses levels of procollagen in mRNA and type II collagen synthesis in cultured human articular and costal chondrocytes. J Biol Chem 261:9049–9056Google Scholar
- 19.Martel-Pelletier J, McCollum R, DiBattista J, Faure M-P, Chin JA, Fournier S et al (1992) The interleukin-1 receptor in normal and osteoarthritic human articular chondrocytes: identification as the type I receptor and analysis of binding kinetics and biologic function. Arthritis Rheum 35:530–540CrossRefPubMedGoogle Scholar
- 28.Fernandes JC, Tardif G, Martel-Pelletier J et al (1999) In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthitic progression. Am J Pathol 154:1535–1544Google Scholar
- 33.Dougados M, Nguyen M, Berdah L et al (2003) Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the chondromodulating effect of diacerein in OA of the hip. Clin Exp Rheumatol 21:152–154Google Scholar
- 35.Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, Loeuille D, Kivits AJ, Silver D, Appleton BE (2009) Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Artthritis Rheum 61:344–352CrossRefGoogle Scholar
- 39.Lane NE, Schnitzer TJ, Smith MD et al (2008) Tanezumab relieves moderate to severe pain due to osteoarthritis of the knee: a phase 2 trial. In: American College of Rheumatology. http://acr.confex.com/acr/2008/webprogram/Paper3546.html
- 40.Pfizer (2008) A phase 3 randomized, double blind, placebo-controlled multicenter study of the analgesic efficacy and safety of tanezumab in patients with osteoarthritis of the knee. In: ClinicalTrials.gov. http://www.clinicaltrials.gov/show/NCT00733902. Accessed 4 Oct 2009
- 41.Pfizer (2008) A phase 3 randomized, double blind, placebo-controlled multicenter study of the analgesic efficacy and safety of tanezumab in patients with osteoarthritis of the hip. In: ClinicalTrials.gov. http://www.clinicaltrials.gov/show/NCT00744471. Acessed 4 Oct 2009