title: Exogenous interleukin-6, interleukin-13, and interferon-γ provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice.
abstract: BACKGROUND
  Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident.
  
  
  METHODS
  To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection.
  
  
  RESULTS
  After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1)-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS). While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only.
  
  
  CONCLUSIONS
  Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.
authors: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Szu-Wei
authors: SW
authors: Huang
authors: Yi-Ping
authors: YP
authors: Lee
authors: Yu-Ting
authors: YT
authors: Hung
authors: Chun-Hung
authors: CH
authors: Lin
authors: Jih-Ing
authors: JI
authors: Chuang
authors: Huan-Yao
authors: HY
authors: Lei
authors: Ih-Jen
authors: IJ
authors: Su
authors: Chun-Keung
authors: CK
authors: Yu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000276:immunology / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000633:toxicity*; D018793:Interleukin-13 / Q000097:blood / Q000633:toxicity*; D015850:Interleukin-6 / Q000097:blood / Q000633:toxicity*; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D010243:Paralysis / Q000276:immunology / Q000473:pathology / Q000821:virology; D011654:Pulmonary Edema / Q000097:blood / Q000276:immunology / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000276:immunology / Q000473:pathology* / Q000821:virology; D014709:Vero Cells
chemical_list: D018793:Interleukin-13; D015850:Interleukin-6; D007371:Interferon-gamma