title: Th1/Th2 cytokine balance and nitric oxide in cerebrospinal fluid and serum from patients with multiple sclerosis.
abstract: Tumor necrosis factor (TNF-alpha) and IL-10 are key regulators of the T helper (Th)1/Th2 balance, which is critically skewed in many pathological conditions including immune-mediated inflammatory diseases of central nervous system (CNS) such as multiple sclerosis (MS). Nitric oxide (NO) has been reported to have dual effects on CNS pathology, and to play an important role in MS. We performed a cross-sectional study in 17 randomly selected patients during MS flare-up, and compared levels of TNF-alpha, IL-10 and NO in serum and cerebrospinal fluid (CSF) with the serum values of these mediators in two different control groups, healthy subjects and HIV-infected untreated patients. Serum and CSF values of TNF-alpha, IL-10 and NO were higher in MS patients than in the serum of healthy controls. Two MS patients showed increased levels of NO in CSF, with inversion of the NO(SERUM)/NO(CSF) quotient, which is clearly indicative of an intrathecal production of NO. No correlation among the values of both cytokines and NO, and the laboratory parameters analysed in MS patients (IgG index, presence of IgG oligoclonal bands and albumin quotient) was found. The high levels of TNF-alpha and IL-10 (both in serum and CSF) accompanying an MS attack suggest a simultaneous expression of Th1 and Th2 cytokines as opposed to sequential expression of Th1 followed by Th2 as described in the models of experimental autoimmune encephalomyelitis (EAE). Globally, our results support the inherent heterogeneity of the disease.
authors.affiliation: Division of Immunology and Neurology, Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, c/ Dr. Esquerdo 46, 28007 Madrid, Spain.
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Rodríguez-Sáinz
authors.forename: Silvia
authors.initials: S
authors.lastname: Sánchez-Ramón
authors.forename: Clara
authors.initials: C
authors.lastname: de Andrés
authors.forename: Margarita
authors.initials: M
authors.lastname: Rodríguez-Mahou
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide