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

Abstract

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.

Litchi–associated Acute Encephalitis in Children, Northern Vietnam, 2004–2009

“…However, in our study, the presence of fever and meningeal symptoms and the absence of high elevation of liver enzyme favor a viral etiology rather than a toxic origin. Additionally, we demonstrated that children with AME harbor elevated levels of type I interferon in serum and interferon-inducible cytokines, such as IL-6 and IL-8 in CSF, compatible with an infectious process ( 16 , 17 ); however, these cytokines are expected to be elevated in any inflammatory process.…”

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

“…This may support the possibility of HHV-6 being the cause of the primary encephalitis in patients later developing temporal lobe epilepsy. HHV-6-associated encephalopathy has been reported [16], however, the connection between viral gene expression and disease pathogenesis remains unclear.…”

Pertussis-associated encephalitis/encephalopathy with marked demyelination in an unimmunized child

“…Using a murine model, it was demonstrated that respiratory infection with B. pertussis resulted in the persistent expression of mRNA transcripts for IL-1β and tumor necrosis factor α, and transient expression of IL-6, and elevated levels of these cytokine proteins in the hippocampus and hypothalamus [11], suggesting that infection at mucosal surfaces results in the induction of pro-inflammatory cytokine production in the brain. Proinflammatory cytokines and chemokines are considered to be associated with the development of acute encephalitis/encephalopathy [12][13][14][15]. The levels of IL-6 and -10 in the CSF in our patient were higher than those in the serum, suggesting that these cytokines may have contributed to the pathogenesis of encephalitis/encephalopathy.…”