Comparison of the levels of human herpesvirus 6 (HHV-6) DNA and cytokines in the cerebrospinal fluid and serum of children with HHV-6 encephalopathy

J Med Virol. 2010 Aug;82(8):1410-5. doi: 10.1002/jmv.21808.


Primary human herpesvirus-6 (HHV-6) infection is a common cause of acute sporadic encephalopathy in Japanese children. Occasionally, HHV-6 is not detected in the cerebrospinal fluid (CSF) of patients with encephalopathy, for example, in those with focal viral encephalitis, such as herpes simplex viral encephalitis. This indicates that HHV-6 encephalopathy is caused by an indirect mechanism, although this is not fully understood. HHV-6 DNA, cytokines (interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor-alpha, interferon-gamma), and matrix metalloproteinase-9 were quantitated in both the CSF and serum of 13 patients with HHV-6 encephalopathy during the acute phase of the disease. HHV-6 DNA was detected in the CSF of seven patients with HHV-6 encephalopathy. The viral DNA concentration was significantly higher in serum than in CSF (mean 1.64 x 10(4) vs. 5.70 x 10(1) copies/ml; P = 0.003). The lack or low level of viral DNA in the CSF samples suggests that direct invasion of the central nervous system by HHV-6 is not the main cause of encephalopathy. Additionally, the IL-10 concentration was significantly higher in serum than in CSF (P < 0.001), whereas there was no significant difference in IL-6 levels between the CSF and serum samples. Interestingly, the IL-8 concentration was significantly higher in CSF than in serum (P = 0.038). The distribution of these cytokines differed between CSF and serum. The high CSF concentration of IL-8 could play an important role in the pathogenesis of encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebrospinal Fluid / immunology*
  • Cerebrospinal Fluid / virology*
  • Child, Preschool
  • Cytokines / cerebrospinal fluid*
  • DNA, Viral / blood
  • DNA, Viral / cerebrospinal fluid
  • Encephalitis, Viral / immunology*
  • Encephalitis, Viral / virology*
  • Female
  • Herpesvirus 6, Human / isolation & purification*
  • Humans
  • Infant
  • Japan
  • Male
  • Matrix Metalloproteinase 9 / cerebrospinal fluid
  • Roseolovirus Infections / immunology*
  • Roseolovirus Infections / virology
  • Viral Load


  • Cytokines
  • DNA, Viral
  • Matrix Metalloproteinase 9