title: Serum and cerebrospinal fluid levels of cytokines in acute encephalopathy associated with human herpesvirus-6 infection.
abstract: Human herpesvirus-6 (HHV-6) is a causative agent of exanthema subitum. The immunological pathogenesis of acute encephalopathy associated with HHV-6 infection is still unclear. We measured the concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and cerebrospinal fluid (CSF) during the acute stage in 15 infants with acute encephalopathy and 12 with febrile seizures associated with HHV-6 infection. The serum IL-6, IL-10, sTNFR1, CSF IL-6, and sTNFR1 levels of infants with encephalopathy who had neurological sequelae (n=9) were significantly higher than those with febrile seizures (p=0.011, 0.043, 0.002, 0.029, and 0.005, respectively). In acute encephalopathy, serum IL-6, sTNFR1, and CSF IL-6 levels in infants with neurological sequelae were significantly higher than those without (n=6) neurological sequelae (p=0.043, 0.026, and 0.029, respectively), and serum IFN-gamma, IL-6, IL-10, and sTNFR1 levels were significantly higher than those in the CSF (p=0.037, 0.037, 0.001, and 0.021, respectively). There were no significant differences in serum or CSF cytokine levels between infants who were positive for HHV-6 DNA in the CSF (n=6) compared to those who were negative (n=9). We suggest that cytokines mediate the pathogenesis of acute encephalopathy associated with HHV-6 infection, and that the elevated levels of serum IL-6, sTNFR1, and CSF IL-6 are important for predicting neurological sequelae.
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. ichiyama@yamaguchi-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichiyama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000208:Acute Disease; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D004660:Encephalitis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005077:Exanthema Subitum / Q000150:complications / Q000276:immunology; D005260:Female; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D011782:Quadriplegia / Q000209:etiology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D003294:Seizures, Febrile / Q000134:cerebrospinal fluid / Q000209:etiology / Q000276:immunology
chemical_list: D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I