@article {Yamaguchi22, author = {Norihiko Yamaguchi and Shiro Ohshima and Mitsuko Umeshita-Sasai and Katsuhiro Nishioka and Hideyuki Kobayashi and Toru Mima and Tadamitsu Kishimoto and Yukihiko Saeki}, title = {Synergistic effect on the attenuation of collagen induced arthritis in tumor necrosis factor receptor I (TNFRI) and interleukin 6 double knockout mice.}, volume = {30}, number = {1}, pages = {22--27}, year = {2003}, publisher = {The Journal of Rheumatology}, abstract = {OBJECTIVE: To evaluate any additive effect on attenuation of collagen induced arthritis (CIA) in tumor necrosis factor receptor I (TNFRI) and interleukin 6 (IL-6) double knockout (DKO) mice. METHODS: CIA was induced in wild-type (Wt), TNFRI knockout (TNFRIKO), IL-6 knockout (IL-6KO), and DKO mice. Comparative studies were performed among these different mouse genotypes observing clinical (incidence, arthritis score), histological, radiologic, and immunological aspects. RESULTS: More than 90\% of the Wt, TNFRIKO, and IL-6KO mice developed definite CIA, while only 20\% of the DKO mice did so. Severity of arthritis, indicated by the arthritis score, was significantly reduced in both the TNFRIKO and IL-6KO mice compared with the Wt mice. Moreover, the severity of arthritis in the DKO mice was significantly reduced compared with each single KO mouse (by arthritis scores; DKO vs TNFRIKO, IL-6KO mice, p \< 0.05). In addition, histological and radiologic changes were also significantly reduced in the DKO mice compared with each single KO mouse (by histological and radiologic scores; DKO vs TNFRIKO, IL-6KO mice, p \< 0.05 and p \< 0.01 respectively). In immunological studies, serum anti-type II collagen (anti-CII) antibody concentrations were significantly decreased in the DKO mice compared with each single KO mouse (DKO vs TNFRIKO, IL-6KO mice, p \< 0.01). CONCLUSION: Simultaneous blockade of TNFRI and IL-6 showed synergistic rather than additive effects on the attenuation of CIA. Combinations of anti-TNF-a and anti-IL-6 therapy may provide clinical benefits for treatment of rheumatoid arthritis compared with therapy against each single cytokine.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/30/1/22}, eprint = {https://www.jrheum.org/content/30/1/22.full.pdf}, journal = {The Journal of Rheumatology} }