Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement

Abstract

Symptoms originating from central nervous system (CNS) are frequently occuring in patients with systemic lupus erythematosus (SLE). Reliable diagnostic markers for this condition are presently lacking. Importantly, CNS involvement in lupus patients is associated with increased morbidity and mortality. The aim of this retrospective evaluate was to study the diagnostic value of cerebrospinal fluid (CSF) cytokine levels in SLE patients with CNS involvement. 34 patients with SLE were hospitalized and investigated for the presence of CNS lupus. These patients were evaluated clinically and with magnetic resonance imaging (MRI) and CSF analyses, as well as with neuropsychiatric tests. 13 patients were found to have CNS lupus whereas another four of the patients fulfilled the criteria for CNS involvement but were excluded from this group due to other causes of CNS involvement. Lastly, in 17 SLE cases, the diagnosis of CNS lupus could not be confirmed. CSF levels of interleukin-6 (IL-6) and IL-8, as well as the CSF/serum IL-6 ratio, were elevated in the CNS lupus group, compared with the 17 SLE patients not fullfilling a diagnosis of cerebral lupus. Interestingly, follow-up of five patients being successfully treated for CNS lupus revealed profound decrease of intrathecal IL-6 levels. These results indicate that analysis of CSF cytokine levels, especially IL-6 and IL-8, may be useful in the diagnostics and possibly follow-up of SLE patients with cerebral lupus.

Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study

“…Given the wide variety of clinical manifestations, it is unlikely that a single pathogenic mechanism is responsible for all of them. In addition to autoantibodies, there is evidence to support the notion that proinflammatory cytokines (31,32) and chemokines (33), which have been identified in cerebrospinal fluid (CSF) from SLE patients with NP disease (31)(32)(33), have a pathogenic role. With regard to autoantibodies, the current data suggest that aPL cause focal NP disease (e.g., stroke, seizures) by promoting intravascular thrombosis (5).…”

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

“…Increased secretion of IL-8 by lupus DCs could potentially contribute to tissue damage, as this cytokine has been proposed to play an important role in the development of lupus nephritis (61)(62)(63)(64) and has been found to be elevated in lupus patients with CNS involvement (65). IL-8 is produced by numerous cell types, including monocytes/macrophages and DCs (64,66,67).…”

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

“…Autoantibodies in the CSF and immunocompetent cells in the choroid plexus of mice (Sakic et al, 2000b;Vogelweid et al, 1991) and the NP-SLE patient are further evidence that the blood-brain barrier in SLE becomes permeable to circulating factors (Abbott et al, 2003). Previous clinical studies had engendered the hypothesis that various brain-reactive antibodies (Denburg et al, 1993), cytokines, and toxic metabolites (Svenungsson et al, 2001;Trysberg et al, 2000) play principal roles in induction of SLEinduced brain damage in general, and gray matter in particular (Steens et al, 2004). With respect to the origin of autoantibodies, one of the important issues is whether they passively diffuse through the damaged blood-brain barrier or are synthesized intrathecally (i.e., within the brain).…”