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




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Respiratory Research

, 12:147

First Online: 01 December 2011Received: 11 August 2011Accepted: 06 November 2011

Abstract

BackgroundNeonatal 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.

MethodsTo 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.

ResultsAfter 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.

ConclusionsExogenous 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.

Keywordsenterovirus 71 pulmonary edema proinflammatory cytokine mouse model List of abbreviationsBSAbovine serum albumin

EV71Enterovirus 71

HSV-1herpes simplex virus-1

PIFpeak of inspiratory flow

PEFpeak of expiratory flow

LCLocus coeruleus

MRImagnetic resonance imaging

MVminute volume

NTSnucleus tractus solitarii

PVpoliovirus

PEpulmonary edema

TVtidal volume.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-147 contains supplementary material, which is available to authorized users.

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Author: Szu-Wei Huang - Yi-Ping Lee - Yu-Ting Hung - Chun-Hung Lin - Jih-Ing Chuang - Huan-Yao Lei - Ih-Jen Su - Chun-Keung Yu

Source: https://link.springer.com/







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