OBJECTIVES: We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS: Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition.
OBJECTIVES: We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS: Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition.
Authors: Ankur Singh; Rachit Agarwal; Carlos A Diaz-Ruiz; Nick J Willett; Peiyi Wang; L Andrew Lee; Qian Wang; Robert E Guldberg; Andrés J García Journal: Adv Healthc Mater Date: 2014-03-31 Impact factor: 9.933
Authors: Cleo S Bonnet; Anwen S Williams; Sophie J Gilbert; Ann K Harvey; Bronwen A Evans; Deborah J Mason Journal: Ann Rheum Dis Date: 2013-10-15 Impact factor: 19.103