Effect of the JAK Inhibitor Baricitinib on Cytokine Production and Bone Properties in a Mouse Model of Accelerated Aging

Age-related osteoporosis is characterized by progressive loss of bone mass and deterioration of bone microarchitecture, leading to enhanced skeletal fragility. Cytokines regulate bone remodeling through distinct signaling pathways. Baricitinib, a selective JAK1/2 inhibitor effective in inflammatory disorders such as rheumatoid arthritis, suppresses cytokine signaling, but its role in age-related osteoporosis remains insufficiently defined. In our study a total of 60 eight-month-old female SAMP8 mice were randomized to receive baricitinib (10 mg/kg) or vehicle twice daily by oral gavage for six weeks. Bone outcomes were evaluated by high-resolution micro-computed tomography (µCT) and static histomorphometry. Intracellular cytokine production by splenocytes was determined via flow cytometry. We found that baricitinib substantially reduced T-cell cytokine production, decreasing IL-6, IL-17, IFN-γ, and IL-21 in CD4⁺ T cells and IL-6 in CD8⁺ T cells, accompanied by lower IFN-γ/IL-17 and IL-21/IL-6 ratios, respectively. µCT analyses showed no significant intergroup differences in BV/TV, whereas histomorphometry demonstrated higher BV/TV in the baricitinib group. Overall, baricitinib was found to effectively suppressed proinflammatory cytokines in aged SAMP8 mice but did not consistently enhance bone parameters, indicating reduced skeletal responsiveness during aging.