title: The clinical correlation of regulatory T cells and cyclic adenosine monophosphate in enterovirus 71 infection.
abstract: BACKGROUND
  Brainstem encephalitis (BE) and pulmonary edema (PE) are notable complications of enterovirus 71 (EV71) infection.
  
  
  OBJECTIVE
  This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.
  
  
  METHODS
  Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD) or BE group, and the autonomic nervous system (ANS) dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP) levels, and the regulatory T cell (Tregs) profiles of the patients were determined.
  
  
  RESULTS
  Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4(+)CD25(+)Foxp3+ and CD4(+)Foxp3(+) T cells compared with patients with HFMD or BE. The expression frequency of CD4-CD8- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.
  
  
  CONCLUSIONS
  These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.
authors.affiliation: Department of Emergency Medicine College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Liao
authors.affiliation: Department of Pediatrics, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
mesh_terms: D001341:Autonomic Nervous System / Q000187:drug effects / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D002675:Child, Preschool; D000242:Cyclic AMP / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003710:Demography; D029821:Enterovirus A, Human / Q000187:drug effects / Q000276:immunology*; D004769:Enterovirus Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000821:virology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D020105:Milrinone / Q000494:pharmacology; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000242:Cyclic AMP; D020105:Milrinone