Correlations of cytokine levels in cerebrospinal fluid and peripheral blood with outcome of HHV-6B encephalitis after hematopoietic stem cell transplantation.

Abstract

Human herpesvirus (HHV)-6B encephalitis has been recognized as a serious complication after allogeneic hematopoietic cell transplantation (allo-HCT). Little is known about the pathogenic mechanism for its progression. We retrospectively evaluated the 16 kinds of cytokines and chemokines in cerebrospinal fluid (CSF) and plasma in patients who developed HHV-6B encephalitis. Among a total of 20 patients, 12 were categorized as the poor prognosis group (died of encephalitis; n=8 and retained sequelae; n=4), and other eight patients were categorized as the good prognosis group (complete recovery; n=8). Concentrations of CSF IL-6 and IL-8 at the onset of encephalitis were significantly higher in the poor prognosis group than in the good prognosis group (median CSF IL-6, 28.27pg/mL vs 14.32pg/mL, P=.004; median CSF IL-8, 128.70pg/mL vs 59.43pg/mL, P=.043). Regarding plasma, the concentration of each cytokine at the onset of encephalitis was not significantly different between the two groups, except IL-5. However, higher levels of IL-6, IL-7, and MCP-1 and lower levels of IL-12 were observed 1week before the development of encephalitis in patients with poor prognosis (median IL-6; 464.17pg/mL vs 47.82pg/mL, P=.02; median IL-12; 1.63pg/mL vs 6.57pg/mL, P=.03). We found that one week before onset of HHV-6B encephalitis, poor prognosis patients had high plasma concentrations of IL-6, IL-7, and MCP-1 and low concentrations of IL-12. At the onset of encephalitis, high concentrations of IL-6 and IL-8 in CSF were more common in the poor prognosis group, consistent with other evidence that IL-6 can have a role in CNS disturbances. Our findings show that specific cytokine status is associated with severe brain damage in patients with HHV-6B encephalitis, demonstrate prognostic value of plasma IL-6 concentrations, and suggest evaluation of anti-cytokine therapeutics in patients with HHV-6B encephalitis.