Increased levels of proinflammatory cytokines and nitric oxide metabolitesin neuropsychiatric lupus erythematosus

Objective-To investigate systemic and intrathecal production of proinflamma tory cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) r elease in patients with neuropsychiatric lupus erythematosus (NPLE). Methods-Thirty patients with NPLE rated as mild, moderate, or severe were s tudied and CSF was obtained from 21 of these. Cytokine mRNA expressing cell s were detected by in situ hybridisation. Soluble cytokines were assessed b y enzyme linked immunosorbent assay (ELISA). Nitrite and nitrate were deter mined by capillary electrophoresis. Results-Patients with NPLE had high numbers of lymphocytes expressing mRNA for tumour necrosis factor alpha (TNF alpha), interferon gamma, and interle ukin 10 in blood. The number of peripheral blood TNF alpha mRNA positive ce lls 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 N PLE disease severity. Conclusion-These data suggest that increased peripheral production of proin flammatory cytokines such as TNF alpha may contribute both to an increased production of NO in the central nervous system and to generation of clinica l NPLE. The data also support the possibility that measurements of NO metab olites in CSF may be of value in the diagnosis of neurological symptoms rel ated to SLE.