Interleukin 6 plays a key role in the development of antigen-induced arthritis.
To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight generations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.
Ohshima
S
S
Department of Medicine III, Osaka University Medical School, Suita City, Osaka 565-0871, Japan.
Saeki
Y
Y
Mima
T
T
Sasai
M
M
Nishioka
K
K
Nomura
S
S
Kopf
M
M
Katada
Y
Y
Tanaka
T
T
Suemura
M
M
Kishimoto
T
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology
D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger