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CNS neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and life-threatening manifestation in patients with systemic lupus erythematosus (SLE). Cytokines are key modulators of immune and inflammatory responses, and altered levels of several cytokines have been detected in SLE. We hypothesized that these cytokines are released locally in the CNS, contributing to neuropsychiatric manifestations of SLE. To test this hypothesis, we studied the serum and cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines and chemokines in SLE patients with and without CNS NPSLE. Serum and CSF concentrations of cytokines and chemokines were analyzed using the Luminex bead array system. We found that CSF concentrations of several proinflammatory cytokines and chemokines were significantly increased in SLE patients with CNS NPSLE compared with SLE patients without CNS NPSLE and healthy controls. CSF concentrations of interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and RANTES in SLE patients with CNS NPSLE were significantly higher than in SLE patients without CNS NPSLE and healthy controls. Serum concentrations of IL-6, IL-8, MCP-1, and RANTES in SLE patients with CNS NPSLE were significantly higher than in SLE patients without CNS NPSLE and healthy controls. Serum concentrations of IL