Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury

Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple o...

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Bibliographic Details
Published inJournal of investigative dermatology Vol. 138; no. 11; pp. 2461 - 2469
Main Authors Harrison, Kathleen A., Romer, Eric, Weyerbacher, Jonathan, Ocana, Jesus A., Sahu, Ravi P., Murphy, Robert C., Kelly, Lisa E., Smith, Townsend A., Rapp, Christine M., Borchers, Christina, Cool, David R., Li, Gengxin, Simman, Richard, Travers, Jeffrey B.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.11.2018
Subjects
Acute Disease
Alcoholic Intoxication
Animals
Burns - immunology
Cell Line
Cytokines - metabolism
Ethanol - metabolism
Female
Hot Temperature
Humans
Inflammation Mediators - metabolism
Keratinocytes - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Activating Factor - metabolism
Platelet Membrane Glycoproteins - genetics
Receptors, G-Protein-Coupled - genetics
Up-Regulation
4-MP
PAF
DNFB
KBM
KBP
PLA2
GPC
PAF-R
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Summary:Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator platelet-activating factor in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic platelet-activating factor generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines, such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury were suppressed in mice lacking platelet-activating factor receptors. Together, these studies provide a potential mechanism and treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator platelet-activating factor.
Bibliography:these two provided equally to this work.
K.A.H., E.R., J.W., J.A.O., R.P.S., L.E.K., T.A.S., C.M.R., C.B., D.R.C., J.B.T. performed experiments and data analysis. R.C.M., R.S., G.L. were involved in data analysis. R.C.M., J.B.T. supervised the study. K.A.H., E.R., J.B.T. wrote the manuscript.
Author Contributions
ISSN:0022-202X
1523-1747
DOI:10.1016/j.jid.2018.04.039