Adalimumab combined with erythropoietin improves recovery from spinal cord injury by suppressing microglial M1 polarization-mediated neural inflammation and apoptosis.

ABSTRACT

OBJECTIVE: Adalimumab (ADM), a humanized antibody against tumour necrosis factor (TNF), is widely applied in treating inflammatory and autoimmune diseases, but its usage in spinal cord injury (SCI) is rarely reported. Hence, this study aimed to explore the effect of ADM with or without erythropoietin (EPO) on microglial polarization, neuroinflammation, neural apoptosis, and functional recovery in SCI. METHODS: Primary microglia were stimulated with lipopolysaccharide (LPS) and then treated with ADM, EPO, or ADM combined with EPO. Then, primary neurons were incubated in the microglial culture medium. SCI rats were established and then treated with ADM, EPO or ADM combined with EPO. RESULTS: ADM suppressed LPS-induced microglial M1 polarization, as reflected by downregulated iNOS and CD86 expression, and neuroinflammation, as reflected by decreased TNF-α, IL-1ß, and IL-6 expression, in a dose-dependent manner. Moreover, ADM inhibited microglia-induced neural apoptosis, as reflected by TUNEL assay results and the expression of apoptotic markers (C-Caspase3 and Bcl2), in a dose-dependent manner. EPO monotherapy displayed an effect similar to that of ADM monotherapy. Furthermore, ADM combined with EPO therapy exhibited greater effects than either monotherapy in terms of inhibiting microglial M1 polarization, neuroinflammation, and neural apoptosis. In vivo experiments confirmed the findings of the in vitro experiments and showed that ADM combined with EPO improved SCI functional recovery and neural injury compared with monotherapy. CONCLUSION: ADM combined with EPO improves recovery from SCI by suppressing microglial M1 polarization-mediated neural inflammation and apoptosis.