title: IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.
abstract: OBJECTIVE
  To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE.
  
  
  METHODS
  52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-α in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-α concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA.
  
  
  RESULTS
  The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-α, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL-8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 × 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 × 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients.
  
  
  CONCLUSIONS
  In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE.
authors: Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan takuyosh@jichi.ac.jp.
authors: T
authors: T
authors: Yoshio
authors: Minami-Otsuka Institute of Technology, Minami-Otsuka Clinic, Tokyo, Japan.
authors: H
authors: H
authors: Okamoto
authors: Department of Clinical Immunology, Dokkyo Medical University, Tochigi, Japan.
authors: K
authors: K
authors: Kurasawa
authors: Dei Clinic, Tochigi, Japan.
authors: Y
authors: Y
authors: Dei
authors: Department of Rheumatology and Infectious Disease, Kitasato University School of Medicine, Kanagawa, Japan.
authors: S
authors: S
authors: Hirohata
authors: Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan.
authors: S
authors: S
authors: Minota
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D054357:Chemokine CXCL10 / Q000097:blood / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor
keywords: Central neuropsychiatric lupus erythematosus; G-CSF; IL-6; IL-8; IP-10; MCP-1; antiribosomal P protein antibodies; cerebrospinal fluid