Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia

Jessica A. Dominguez, Paul J. Vithayathil, Ludmila Khailova, Christopher P. Lawrance, Alexandr J. Samocha, Enjae Jung, Ann M. Leathersich, W. Michael Dunne, Craig M. Coopersmith

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P <0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalShock
Volume36
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Pseudomonas aeruginosa
Pneumonia
Wounds and Injuries
Intestines
Apoptosis
Fatty Acid-Binding Proteins
Lung
Mortality
Enterocytes
Transgenic Mice
Therapeutics
Pathology
Cytokines
Kidney

Keywords

  • epidermal growth factor
  • intestine
  • pneumonia
  • Pseudomonas aeruginosa
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Dominguez, J. A., Vithayathil, P. J., Khailova, L., Lawrance, C. P., Samocha, A. J., Jung, E., ... Coopersmith, C. M. (2011). Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia. Shock, 36(4), 381-389. https://doi.org/10.1097/SHK.0b013e31822793c4

Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia. / Dominguez, Jessica A.; Vithayathil, Paul J.; Khailova, Ludmila; Lawrance, Christopher P.; Samocha, Alexandr J.; Jung, Enjae; Leathersich, Ann M.; Dunne, W. Michael; Coopersmith, Craig M.

In: Shock, Vol. 36, No. 4, 10.2011, p. 381-389.

Research output: Contribution to journalArticle

Dominguez, JA, Vithayathil, PJ, Khailova, L, Lawrance, CP, Samocha, AJ, Jung, E, Leathersich, AM, Dunne, WM & Coopersmith, CM 2011, 'Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia', Shock, vol. 36, no. 4, pp. 381-389. https://doi.org/10.1097/SHK.0b013e31822793c4
Dominguez, Jessica A. ; Vithayathil, Paul J. ; Khailova, Ludmila ; Lawrance, Christopher P. ; Samocha, Alexandr J. ; Jung, Enjae ; Leathersich, Ann M. ; Dunne, W. Michael ; Coopersmith, Craig M. / Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia. In: Shock. 2011 ; Vol. 36, No. 4. pp. 381-389.
@article{34f0e4746f254f4bb7910d94514c52e0,
title = "Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia",
abstract = "Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65{\%} to 10{\%} when initiated immediately after the onset of pneumonia and to 27{\%} when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50{\%} vs. 28{\%}, respectively, P <0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.",
keywords = "epidermal growth factor, intestine, pneumonia, Pseudomonas aeruginosa, Sepsis",
author = "Dominguez, {Jessica A.} and Vithayathil, {Paul J.} and Ludmila Khailova and Lawrance, {Christopher P.} and Samocha, {Alexandr J.} and Enjae Jung and Leathersich, {Ann M.} and Dunne, {W. Michael} and Coopersmith, {Craig M.}",
year = "2011",
month = "10",
doi = "10.1097/SHK.0b013e31822793c4",
language = "English (US)",
volume = "36",
pages = "381--389",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia

AU - Dominguez, Jessica A.

AU - Vithayathil, Paul J.

AU - Khailova, Ludmila

AU - Lawrance, Christopher P.

AU - Samocha, Alexandr J.

AU - Jung, Enjae

AU - Leathersich, Ann M.

AU - Dunne, W. Michael

AU - Coopersmith, Craig M.

PY - 2011/10

Y1 - 2011/10

N2 - Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P <0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

AB - Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P <0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

KW - epidermal growth factor

KW - intestine

KW - pneumonia

KW - Pseudomonas aeruginosa

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=80052967969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052967969&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e31822793c4

DO - 10.1097/SHK.0b013e31822793c4

M3 - Article

C2 - 21701422

AN - SCOPUS:80052967969

VL - 36

SP - 381

EP - 389

JO - Shock

JF - Shock

SN - 1073-2322

IS - 4

ER -