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Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus
  1. E Svenungssona,
  2. M Anderssonb,c,
  3. L Brundinb,
  4. R van Vollenhovena,
  5. M Khademic,
  6. A Tarkowskid,
  7. D Greitze,
  8. M Dahlströmc,
  9. I Lundberga,
  10. L Klareskoga,
  11. T Olssonb,c
  1. aDepartment of Medicine, Rheumatology Unit, Karolinska Hospital, Stockholm, Sweden, bDepartment of Neurology, Karolinska Hospital, cDepartment of Medicine, Neuroimmunology Unit, Karolinska Hospital, dDepartment of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden, eMR Research Centre, Department of Neuroradiology, Karolinska Hospital
  1. Dr E Svenungsson, Department of Rheumatology, Karolinska Hospital, S-171 76 Stockholm, SwedenElisabet.Svenungsson{at}medks.ki.se

Abstract

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 α (ΤΝFα), interferon γ, and interleukin 10 in blood. The number of peripheral blood TNFα mRNA positive cells correlated strongly with the level of NO metabolites in the CSF (r 2=0.69). Both the number of peripheral blood mononuclear cells expressing mRNA for TNFα 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 TNFα 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.

  • neuropsychiatric systemic lupus erythematosus
  • nitric oxide
  • tumour necrosis factor α
  • cerebrospinal fluid

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