Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema

J Infect Dis. 2003 Aug 15;188(4):564-70. doi: 10.1086/376998. Epub 2003 Jul 23.


Taiwan experienced several epidemics of enterovirus 71 (EV71) infections, which were associated with brainstem encephalitis (BE) and pulmonary edema (PE). To elucidate the role of immune mechanisms in the pathogenesis of BE caused by EV71 and its fatal complication, PE, we analyzed the laboratory findings, cytokine, and immunophenotypes of 73 EV71-infected patients with BE. Patients were stratified by disease: PE (n=14), autonomic nervous system (ANS) dysregulation (n=25), and isolated BE (n=34). The mortality rate for PE was 64.3%. Leukocytosis and thrombocytosis were significantly more frequent among patients with PE. A significant elevation of plasma interleukin (IL)-10, IL-13, and interferon (IFN)-gamma levels observed in patients with PE. Patients with PE also had lower circulating CD4(+) T cells, CD8(+) T cells, and natural killer (NK) cells. An extensive peripheral and central nervous system inflammatory response with abnormal IL-10, IL-13, and IFN-gamma cytokine production and lymphocyte depletion appears to be responsible for the pathogenesis of EV71-associated PE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Stem / immunology
  • Brain Stem / pathology
  • Brain Stem / virology*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Child, Preschool
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Encephalitis, Viral / complications
  • Encephalitis, Viral / immunology*
  • Encephalitis, Viral / pathology
  • Encephalitis, Viral / virology*
  • Enterovirus / isolation & purification*
  • Enterovirus Infections / complications
  • Enterovirus Infections / immunology*
  • Enterovirus Infections / pathology*
  • Female
  • Humans
  • Infant
  • Interleukins / metabolism
  • Killer Cells, Natural / immunology
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Male
  • Pulmonary Edema / complications*
  • Pulmonary Edema / immunology


  • Cytokines
  • Interleukins