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@article{Wilson:2017:10.3389/fimmu.2017.00128,
author = {Wilson, MR and Wakabayashi, K and Bertok, S and Oakley, C and Patel, BV and O'Dea, KP and Cordy, JC and Morley, PJ and Bayliffe, AI and Takata, M},
doi = {10.3389/fimmu.2017.00128},
journal = {Frontiers in Immunology},
title = {Inhibition of TNF receptor p55 by a domain antibody attenuates the initial phase of acid-induced lung injury in mice},
url = {http://dx.doi.org/10.3389/fimmu.2017.00128},
volume = {8},
year = {2017}
}

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TY  - JOUR
AB  - Background: Tumor necrosis factor-α (TNF) is strongly implicated in the development ofacute respiratory distress syndrome (ARDS), but its potential as a therapeutic target has beenhampered by its complex biology. TNF signals through two receptors, p55 and p75, whichplay differential roles in pulmonary edema formation during ARDS. We have recentlyshown that inhibition of p55 by a novel domain antibody (dAb™) attenuated ventilator36induced lung injury. In the current study we explored the efficacy of this antibody in mousemodels of acid-induced lung injury, to investigate the longer consequences of treatment.Methods: We employed two acid-induced injury models, an acute ventilated model and aresolving spontaneously breathing model. C57BL/6 mice were pretreated intratracheally orintranasally with p55-targeting dAb or non-targeting ‘dummy’ dAb, 1 or 4 hours before acidinstillation.Results: Acid instillation in the dummy dAb group caused hypoxemia, increased respiratorysystem elastance, pulmonary inflammation and edema in both the ventilated and resolvingmodels. Pretreatment with p55-targeting dAb significantly attenuated physiological markersof ARDS in both models. p55-targeting dAb also attenuated pulmonary inflammation in theventilated model, with signs that altered cytokine production and leukocyte recruitmentpersisted beyond the very acute phase.Conclusions: These results demonstrate that the p55-targeting dAb attenuates lung injury andedema formation in models of ARDS induced by acid aspiration, with protection from asingle dose lasting up to 24 hours. Together with our previous data, the current study lends support towards the clinical targeting of p55 for patients with, or at risk of ARDS.
AU  - Wilson,MR
AU  - Wakabayashi,K
AU  - Bertok,S
AU  - Oakley,C
AU  - Patel,BV
AU  - O'Dea,KP
AU  - Cordy,JC
AU  - Morley,PJ
AU  - Bayliffe,AI
AU  - Takata,M
DO  - 10.3389/fimmu.2017.00128
PY  - 2017///
SN  - 1664-3224
TI  - Inhibition of TNF receptor p55 by a domain antibody attenuates the initial phase of acid-induced lung injury in mice
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2017.00128
UR  - http://hdl.handle.net/10044/1/44245
VL  - 8
ER  -

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