To understand the contribution of IL-6/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of
tocilizumab on those abnormalities, we evaluated early change in a
collagen-induced arthritis (CIA) monkey model with or without a single administration of
tocilizumab. Six CIA cynomolgus monkeys received
tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were analyzed using HE,
silver impregnation (SI), or immunohistochemistry (RANKL) staining. The number of osteoclasts increased in the
arthritis control but was suppressed in the
tocilizumab-treated animals. Osteoblast/stromal cells of the
arthritis control monkeys were of monolayer, while in the
tocilizumab-treated monkeys, the cells were multi-layer or differentiated osteoblasts, and the meshwork of the reticulum fibers showed recovery in the SI. Hematopoietic marrow was replaced by interstitial fluid and reticulum fibers were eliminated in the arthritic model but showed recovery in the
tocilizumab-treated animals. RANKL showed overproduction with
arthritis and suppressed with
tocilizumab treatment. The evidence indicates that IL-6/IL-6R is involved in subchondral bone and bone marrow change in RA patients.
Tocilizumab treatment recovered changes in the CIA monkeys as a result of the co-differentiation between the osteoclasts and the osteoblast/stramal cells, at least partially through the suppression of RANKL overproduction.