Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated Brainstem encephalitis

Background. Brainstem encephalitis (BE) is a serious neurological complication of enterovirus 71 (EV71) infection. The present study was designed to determine the characteristics of the chemokine response in the blood and cerebrospinal fluid (CSF) of patients with EV71-associated BE. Methods. Thirty-one patients with BE were studied. They consisted of 12 with uncomplicated BE, 9 with autonomic nervous system (ANS) dysregulation, and 10 with pulmonary edema (PE); 13 healthy control subjects were also studied. Plasma and CSF concentrations of various chemokines were determined by a particle-based flow cytometry immunoassay. Results. Plasma levels of interferon (IFN)-gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by IFN-gamma(MIG), and interleukin (IL)-8 were significantly higher in patients with PE than in those with uncomplicated BE. CSF levels of MIG were significantly higher in patients with PE than in those with uncomplicated BE and ANS dysregulation. The ratios of mean CSF to plasma levels for MCP-1 and IL-8 were highest in patients with uncomplicated BE and tended to fall with increasing severity of the disease. Conclusions. Overexpression of the chemokine cascade in the central nervous system compartment appears to play an important role in the elicitation of the immune response to EV71. The chemokine CSF to plasma ratios suggest that IL-8, IP-10, MCP-1, and possibly MIG-but not RANTES-are synthesized in the brain in response to encephalitis.