Abstract
To assess the potential use of hyaluronic acid (HA) as adjuvant therapy in rheumatoid arthritis, the anti-inflammatory and chondroprotective effects of HA were analysed in experimental rat antigen-induced arthritis (AIA). Lewis rats with AIA were subjected to short-term (days 1 and 8, n = 10) or long-term (days 1, 8, 15 and 22, n = 10) intra-articular treatment with microbially manufactured, high-molecular-weight HA (molecular weight, 1.7 × 106 Da; 0.5 mg/dose). In both tests, 10 buffer-treated AIA rats served as arthritic controls and six healthy animals served as normal controls. Arthritis was monitored by weekly assessment of joint swelling and histological evaluation in the short-term test (day 8) and in the long-term test (day 29). Safranin O staining was employed to detect proteoglycan loss from the epiphyseal growth plate and the articular cartilage of the arthritic knee joint. Serum levels of IL-6, tumour necrosis factor alpha and glycosaminoglycans were measured by ELISA/kit systems (days 8 and 29). HA treatment did not significantly influence AIA in the short-term test (days 1 and 8) but did suppress early chronic AIA (day 15, P < 0.05); however, HA treatment tended to aggravate chronic AIA in the long-term test (day 29). HA completely prevented proteoglycan loss from the epiphyseal growth plate and articular cartilage on day 8, but induced proteoglycan loss from the epiphyseal growth plate on day 29. Similarly, HA inhibited the histological signs of acute inflammation and cartilage damage in the short-term test, but augmented acute and chronic inflammation as well as cartilage damage in the long-term test. Serum levels of IL-6, tumour necrosis factor alpha, and glycosaminoglycans were not influenced by HA. Local therapeutic effects of HA in AIA are clearly biphasic, with inhibition of inflammation and cartilage damage in the early chronic phase but with promotion of joint swelling, inflammation and cartilage damage in the late chronic phase.
Highlights
Rheumatoid arthritis (RA), a chronic systemic disease primarily affecting the joints, is characterised by progressive destruction of cartilage and bony structures of the joints [1,2]
After a plateau between day 0 and day 8 in both untreated rats and HAtreated antigen-induced arthritis (AIA) rats, the body weight rose in concomitance with the decrease of arthritis severity
Joint swelling On day 1, AIA developed as a significant swelling of the right knee joint in all animals (Fig. 2)
Summary
Rheumatoid arthritis (RA), a chronic systemic disease primarily affecting the joints, is characterised by progressive destruction of cartilage and bony structures of the joints [1,2]. Arthritis Research & Therapy Vol 7 No 3 Roth et al. Hyaluronic acid (HA) is a large linear glycosaminoglycan composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine, linked via the 1–4 position of the sugar rings [4]. Inflammatory changes lead to depolymerisation of HA, resulting in a decrease of its molecular weight and its concentration [6]. Its lubricant properties decrease, contributing to the destruction of cartilage and bone [7]
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