Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus

Objective-To investigate systemic and intrathecal production of proinflammatory cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) release in patients with neuropsychiatric lupus erythematosus (NPLE). Methods-Thirty patients with NPLE rated as mild, moderate, or severe were studied and CSF was obtained from 21 of these. Cytokine mRNA expressing cells were detected by in situ hybridisation. Soluble cytokines were assessed by enzyme linked immunosorbent assay (ELISA). Nitrite and nitrate were determined by capillary electrophoresis. Results-Patients with NPLE had high numbers of lymphocytes expressing mRNA for tumour necrosis factor alpha (TNF alpha), interferon gamma, and interleukin 10 in blood. The number of peripheral blood TNF alpha mRNA positive cells correlated strongly with the revel of NO metabolites in the CSF (r(2)=0.69). Both the number of peripheral blood mononuclear cells expressing mRNA for TNF alpha as well as the CSF level of NO metabolites correlated with NPLE disease severity. Conclusion-These data suggest that increased peripheral production of proinflammatory cytokines such as TNF alpha may contribute both to an increased production of NO in the central nervous system and to generation of clinical NPLE. The data also support the possibility that measurements of NO metabolites in CSF may be of value in the diagnosis of neurological symptoms related to SLE.