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Epidermal growth factor preserves intestinal integrity and decreases mortality in a murine model of Pseudomonas aeruginosa pneumonia
Author(s) -
Clark Jessica Ann,
Lawrance Christopher P.,
Dunne William M.,
Coopersmith Craig M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1189.4
Subject(s) - sepsis , epidermal growth factor , apoptosis , pneumonia , medicine , saline , gastroenterology , andrology , biology , pathology , immunology , receptor , biochemistry
Exogenous epidermal growth factor (EGF) attenuates intestinal injury and decreases mortality in a peritonitis model. However, the role of EGF in sepsis caused by extraabdominal infection is unknown. We hypothesized that EGF preserves intestinal integrity and decreases mortality in P. aeruginosa pneumonia‐induced sepsis. FVB/N mice were intratracheally injected with 40 μl of 0.6 McF P. aeruginosa and treated with or without EGF (150 ug/kg/d i.p.; n=9/group). Controls were injected with saline (n=5). All mice received antibiotics. At 24 hr, intestines were evaluated for apoptosis by caspase‐3 staining, proliferation by BrdU staining, and villus length. Survival studies were done in a separate cohort of mice (n=5–10/group). Compared to shams, septic mice had increased intestinal apoptosis (36 ± 3 vs. 17 ± 3 cells/100 crypts; p<0.001) and decreased proliferation (502 ± 51 vs. 959 ± 43 cells/100 crypts; p<0.001), while EGF normalized both to sham levels (21 ± 1 vs. 17 ± 3 and 886 ± 64 vs. 959 ± 43 cells/100 crypts, respectively; p=ns). Septic mice had shorter villi compared to shams, and EGF treatment resulted in normalization to sham villi lengths (333 ± 15 vs. 415 ± 30 vs. 432 ± 19 μ m; p<0.01 and p=ns). At 7 days, septic EGF treated mice had a survival advantage compared to septic mice (92% vs. 50%; p=0.05). EGF preserves intestinal integrity and improves survival in pneumonia‐induced sepsis; thus, the protective effects of EGF are not specific to the anatomical site or type of infection. EGF may be a novel therapeutic agent for the treatment of sepsis.