Antigen induced arthritis (AIA) can be transferred by bone marrow transplantation: evidence that interleukin 6 is essential for induction of AIA.
OBJECTIVE
To investigate the role of bone marrow cells (BMC) in the induction of antigen induced arthritis (AIA), the expression of 3 major proinflammatory cytokines, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, was examined in the bone marrow (BM) of mice with AIA. We also examined whether AIA could be transferred by bone marrow transplantation (BMT).


METHODS
Expression of IL-1beta, TNF-alpha, and IL-6 in BMC was assessed by immunohistochemistry throughout the course of AIA. BMT experiments were performed using 2 different mouse genotypes, wild type (IL-6+/+) and IL-6 deficient (IL-6-/-) mice, as a donor. The gradation of AIA was evaluated histologically.


RESULTS
IL-6 was highly expressed in the BM at induction as well as during progression of AIA, while TNF-alpha showed a marginal expression, and no significant expression of IL-1beta was detected throughout the course of AIA. In BMT experiments, all irradiated IL-6+/+ mice developed typical AIA by transplantation of BMC from immunized IL-6+/+ mice, whereas almost no irradiated IL- 6+/+ mice transplanted with BMC from the immunized IL-6-/- mice developed definite arthritis.


CONCLUSIONS
These results suggest that BMC play a critical role and IL-6 is a key cytokine for the induction and progression of AIA. There may be clinical benefits in the blockade of IL-6 and BMT in the treatment of rheumatoid arthritis.
Kobayashi
Hideyuki
H
Department of Molecular Medicine, Osaka University Medical School, Japan.
Ohshima
Shiro
S
Nishioka
Katsuhiro
K
Yamaguchi
Norihiko
N
Umeshita-Sasai
Mitsuko
M
Ishii
Taeko
T
Mima
Toru
T
Kishimoto
Tadamitsu
T
Kawase
Ichiro
I
Saeki
Yukihiko
Y
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha