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

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)-1 beta, 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. J. Med. Virol. 82:1410-1415, 2010. (C) 2010 Wiley-Liss, Inc.