Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema.
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.
Wang
Shih-Min
SM
Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
Lei
Huan-Yao
HY
Huang
Kao-Jean
KJ
Wu
Jing-Ming
JM
Wang
Jen-Ren
JR
Yu
Chun-Keung
CK
Su
Ih-Jen
IJ
Liu
Ching-Chuan
CC
D001933:Brain Stem / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D018792:Encephalitis, Viral / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004770:Enterovirus / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D011654:Pulmonary Edema / Q000150:complications* / Q000276:immunology
D016207:Cytokines; D007378:Interleukins