RT Journal Article
SR Electronic
T1 Synergistic effect on the attenuation of collagen induced arthritis in tumor necrosis factor receptor I (TNFRI) and interleukin 6 double knockout mice.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 22
OP 27
VO 30
IS 1
A1 Yamaguchi, Norihiko
A1 Ohshima, Shiro
A1 Umeshita-Sasai, Mitsuko
A1 Nishioka, Katsuhiro
A1 Kobayashi, Hideyuki
A1 Mima, Toru
A1 Kishimoto, Tadamitsu
A1 Saeki, Yukihiko
YR 2003
UL http://www.jrheum.org/content/30/1/22.abstract
AB 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.