Open Access Open Badges Research

Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

Szu-Wei Huang1, Yi-Ping Lee2, Yu-Ting Hung2, Chun-Hung Lin3, Jih-Ing Chuang3, Huan-Yao Lei15, Ih-Jen Su456 and Chun-Keung Yu157*

Author Affiliations

1 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

3 Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

4 Department of Clinical Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan

5 Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan

6 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan

7 National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan

For all author emails, please log on.

Respiratory Research 2011, 12:147  doi:10.1186/1465-9921-12-147

Published: 6 November 2011



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.


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.


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.


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.

enterovirus 71; pulmonary edema; proinflammatory cytokine; mouse model