Interleukin‐6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus

Abstract

Objective. To define the cytokine and chemokine profile in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Methods. Forty-two SLE patients who had been hospitalized because of NP manifestations were studied. Patients were evaluated at hospitalization and 6 months later; a CSF sample was obtained at each evaluation. As controls, CSF from 6 SLE patients with septic meningitis, 16 SLE patients with no history of NP manifestations (non-NPSLE), and 25 patients with nonautoimmune diseases were also studied. Results. CSF levels of the following molecules were significantly increased in NPSLE patients as compared with non-NPSLE and nonautoimmune diseases control patients, respectively: IL-6 (32.7 versus 3.0 and 2.96 pg/ml), IL-8 (102.8 versus 29.97 and 19.7 pg/ml), IP-10 (888.2 versus 329.7 [P not significant] and 133.6 pg/ml), RANTES (3.8 versus 2.5 and 2.2 pg/ml), MCP-1 (401.7 versus 257.9 [P not significant] and 136.9 pg/ml), and MIG (35.4 versus 11.4 and 3.5 pg/ml). Low levels of IL-2, IL-4, IL-10, TNF␣, and IFN␥ were found in all groups. All cytokines and chemokines, except TNF␣, were significantly higher among the SLE patients with septic meningitis than among the NPSLE patients. Six months later and in the absence of NP manifestations, all elevated molecule levels, except RANTES, in patients with NPSLE had decreased significantly, and no differences were noted between the NPSLE and non-NPSLE groups.Conclusion. A central nervous system response composed of IL-6 and chemokines, but not Th1/Th2 cytokines, is associated with NP manifestations in SLE patients.

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).…”

Pathogenesis of neurocognitive and neuropsychiatric manifestations in childhood-onset lupus: an overview

“…109,110 Overexpression of genes encoding the proinflammatory cytokines, interleukin-1β, interleukin-6 and interferon-γ, have been demonstrated in the hippocampi of MRL-lpr/lpr SLE mice. Atrophy and increased apoptosis in the hippocampi of these mice has also been reported.…”

Actualización en lupus neuro-psiquiátrico con énfasis en déficit cognitivo

“…Además, los síntomas de LESNP se han asociado con la presencia de niveles elevados de proteínas inflamatorias interferón e interleuquina 6 (IL-6) en suero y en LCR [56][57][58] . Su presencia en LCR podría significar un peor pronóstico del los síntomas NP 59 .…”