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 a (TNF[Alpha]), interferon [Gamma], and interleukin 10 in blood. The number of peripheral blood TNF[Alpha] mRNA positive cells correlated strongly with the level of NO metabolites in the CSF ([r.sup.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.
(Ann Rheum Dis 2001;60:372-379)
Neuropsychiatric manifestations of systemic lupus are common and may affect up to two thirds of patients with systemic lupus erythematosus (SLE).[1 2] There is a diversity of manifestations from both the central nervous system and the peripheral nervous system, such as fatigue, headache, cognitive dysfunction, mood/anxiety syndromes, psychoses, seizures, stroke, and neuropathies. Thus the diagnosis of neuropsychiatric lupus erythematosus (NPLE) is difficult because it may mimic other neurological diseases. Recently the American College of Rheumatology (ACR) proposed a standardised nomenclature system for neuropsychiatric symptoms of SLE, which may facilitate further studies on NPLE.
Explanations for neurological manifestations in SLE include damage to the nervous system mediated by autoantibodies and immune complexes.[4 5] There is also evidence that vascular lesions in patients with SLE, both cerebral and others, are associated with the occurrence of antiphospholipid antibodies. Thus several recent studies have divided patients with NPLE into two groups, one consisting of patients with focal vascular lesions and antiphospholipid antibodies, and the other of patients with diffuse neurological symptoms without antiphospholipid antibodies.[7 8] However, there is a significant overlap between these two groups, with an overrepresentation of antiphospholipid antibody positivity among patients with diffuse NPLE as well. Furthermore, there is evidence that antiphospholipid antibodies in NPLE may have other pathogenetic roles besides being thrombogenic.[9 10]
Another possible pathophysiological mechanism in NPLE is related to the direct or indirect effects of inflammatory mediators on the nervous system. Proinflammatory cytokines produced both outside and inside the central nervous system are known to have dramatic effects on the nervous system, perhaps best described in infections, but local production of cytokines has also been shown to be of importance in primary aseptic neuroinflammatory diseases. Earlier studies have reported increased levels of interleukin 1 (IL1), interleukin 6 (IL6), and...