Anti-IL-6 receptor antibody suppresses onset of paralytic symptoms in AQP4 peptide-immunized mice without lowering bone strength or mineral density.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by the production of autoantibodies against aquaporin-4 (AQP4). Treatment with prednisolone (PSL) or anti-IL-6 receptor (IL-6R) antibody can reduce the frequency of relapse in patients with AQP4 antibody-positive NMOSD. We previously established a mouse model of paralysis induced by intradermal immunization with AQP4 peptide. In this study, we investigated the effects of PSL and anti-IL-6R antibody treatment on paralysis and on bone fragility in this NMOSD mouse model. Prednisolone and anti-IL-6R antibody treatment each suppressed the clinical scores and incidence of paralytic symptoms in AQP4 peptide-immunized mice. High-PSL treatment induced thinning of cortical bone and reduction of tissue mineral density in the femoral shaft and a decrease in femoral bone strength, although it increased bone volume/tissue volume in the trabecular bone of the distal femur. In contrast, anti-IL-6R treatment showed no significant differences in bone strength or cortical thickness compared to the non-immunized naive group. Bone morphometric analysis showed that high-PSL treatment reduced the bone formation rate in both cortical and trabecular bone, with a predominance of bone resorption, whereas anti-IL-6R treatment demonstrated no notable effect on bone metabolism. These results suggest that anti-IL-6R antibody can prevent the development of paralytic symptoms in AQP4 peptide-immunized mice without reducing bone strength.