Exogenous interleukin-6, interleukin-13, and interferon-γ provoke pulmonary abnormality with mild edema in...

Area of Science:

• Virology
• Immunology
• Neurology

Background:

• Neonatal mice infected with Enterovirus 71 (EV71) strain MP4 exhibited neurological disease and pulmonary dysfunction.
• Severe human EV71 infections typically feature pulmonary edema (PE), which was not observed in these initial mouse models.

Purpose of the Study:

• To investigate if a proinflammatory cytokine response is necessary for EV71-induced pulmonary edema.
• To determine the role of specific cytokines in the pathogenesis of EV71 infection.

Main Methods:

• Neonatal mice were infected intracranially with EV71/MP4.
• Exogenous pro-inflammatory cytokines (IL-6, IL-13, IFN-γ) were administered to infected mice during the late stage of infection.
• Adult mice received intracerebral microinjections of EV71 into the nucleus tractus solitarii (NTS) to assess PE development.

Main Results:

• EV71 infection led to hind-limb paralysis, pulmonary dysfunction, and emphysema in neonatal mice.
• Serum levels of IL-6, IL-10, IL-13, and IFN-γ transiently increased post-infection.
• Administration of IL-6, IL-13, and IFN-γ induced mild PE and exacerbated pulmonary abnormalities in EV71-infected mice, but not in controls.
• Adult mice did not develop PE, and neuronal loss was confined to the ventral medulla.

Conclusions:

• Exogenous IL-6, IL-13, and IFN-γ can induce mild pulmonary edema and worsen lung abnormalities in EV71-infected mice.
• The development of classic pulmonary edema symptoms in EV71 infection may require additional factors, potentially including over-activation of the sympathetic nervous system.