Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients with human herpesvirus 6B‐associated acute encephalopathy with biphasic seizures and late reduced diffusion

Abstract

Acute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV-6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)-10 (P = 0.007) and IL-8 (P = 0.025) were significantly higher in the patients with the disease than controls. Serum IL-1β (P = 0.034) and monocyte chemoattractant protein (MCP)-1 (P = 0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL-10 (P = 0.012), regulated on activation normal T cell expressed and secreted (RANTES; P = 0.001), and monokine induced by interferon γ (MIG; P = 0.001) were significantly higher in serum than CSF, meanwhile IL-6 (P = 0.034), IL-8 (P = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum. Additionally, serum IL-10 was significantly higher in the disease patients with sequelae than those without sequelae (P = 0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system.

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

“…Since the KR4 antibody recognizes a late viral protein, cells within the ganglia are likely to be lytically infected. Cytokine dysregulation is generally associated with roseolovirus reactivation in patients with acute illness ( 63 – 65 ). Cells in the peripheral nervous system express surface receptors allowing them to respond to cytokines ( 66 , 67 ).…”

Clinical impact of primary infection with roseoloviruses

“…Severe neurologic sequelae such as acute necrotizing encephalitis, hemorrhagic shock and acute encephalopathy with biphasic seizures complicate nearly half of those cases [38, 39]. Evidence suggests that this may be a cytokine-mediated disorder [40]. HHV-6B has also been implicated in triggering potentially fatal neurologic deterioration in children with an underlying mitochondrial disorder involving polymerase gamma gene (POLG) mutations, suggesting that underlying host factors may contribute to the severity of HHV-6-associated neurological disease [41].…”

Peripheral inflammation increases seizure susceptibility via the induction of neuroinflammation and oxidative stress in the hippocampus

“…Status epilepticus is a common neurological emergency with considerable morbidity, mortality, and associated health-care costs. Emerging clinical and experimental evidence indicates that neuroinflammation with activated microglia and increased production of proinflammatory cytokines is involved in the pathophysiology of epilepsy [ 1 – 6 ]. Not only neuroinflammation is a shared feature of epileptic foci in the human brain and animal models [ 1 – 4 ], conditions that induce neuroinflammation and cytokine production facilitate seizure acquisition and epileptogenesis [ 5 , 6 ].…”

“…Emerging clinical and experimental evidence indicates that neuroinflammation with activated microglia and increased production of proinflammatory cytokines is involved in the pathophysiology of epilepsy [ 1 – 6 ]. Not only neuroinflammation is a shared feature of epileptic foci in the human brain and animal models [ 1 – 4 ], conditions that induce neuroinflammation and cytokine production facilitate seizure acquisition and epileptogenesis [ 5 , 6 ]. Tissue oxidative stress, resultant from an imbalance between production over degradation of the reactive oxygen species (ROS), is another confounding factor in epilepsy [ 7 , 8 ].…”