title: Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis.
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 x 10(6) 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.
authors.affiliation: Department of Orthopaedics, Rudolf-Elle Hospital, Friedrich Schiller University Jena, Eisenberg, Germany. ajroth@gmx.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Roth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mollenhauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
authors.forename: Reneè
authors.initials: R
authors.lastname: Fuhrmann
authors.forename: Albrecht
authors.initials: A
authors.lastname: Straub
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Venbrocks
authors.forename: Peter
authors.initials: P
authors.lastname: Petrow
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.forename: Jörg
authors.initials: J
authors.lastname: Ozegowski
authors.forename: Gundela
authors.initials: G
authors.lastname: Peschel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Müller
authors.forename: Raimund W
authors.initials: RW
authors.lastname: Kinne
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D006820:Hyaluronic Acid