Alendronate alleviates the symptoms of experimental autoimmune encephalomyelitis

Abstract

Nitrogen-containing bisphosphonates, such as alendronate, have been widely used to treat osteoporosis because they may target multiple signals in the mevalonate cascade. The present study evaluated the therapeutic effects of alendronate on experimental autoimmune encephalomyelitis (EAE), which is a prototypical autoimmune disease model. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. The mice were checked daily for clinical symptoms, such as paralysis, and the levels of inflammatory cytokines were analyzed using ELISA, western blot analyses, and immunohistochemistry. The daily oral administration of alendronate to EAE-induced mice significantly reduced the severity of paralysis and lowered T cell proliferation. Additionally, histopathological examinations confirmed that alendronate mitigated inflammation in the spinal cord after EAE induction, suppressed the infiltration of CD68-positive inflammatory cells, and reduced the production of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, as well as inducible nitric oxide synthase (iNOS). Furthermore, the alendronate-treated group exhibited a decrease in the number of iNOS-positive inflammatory cells compared to the vehicle-treated group. Taken together, the present results suggest that alendronate alleviated neuro-inflammation in the spinal cords of EAE-induced mice, which is an animal model of multiple sclerosis, possibly by inhibiting the downstream effects of the mevalonate cascade.