Abstract | PURPOSE: Animal milk fat globule- EGF factor 8 (MFG-E8) has been shown to be beneficial in attenuating the inflammatory response in sepsis. In this study, we examined the effect of recombinant human MFG-E8 (rhMFG-E8) in an animal model of sepsis in an effort to develop it as a potential therapy against sepsis in humans. METHODS: Rats were subjected to sepsis by cecal ligation and puncture (CLP), and at 5 h post-CLP, they were given different doses of rhMFG-E8 (20, 40, 80, 160 μg/kg BW) in normal saline. At 20 h post-CLP, samples were collected for further analysis. A 10-day survival study was also performed. RESULTS: At 20 h after CLP, organ injury indicators, serum IL-6 and TNF-α, and plasma HMGB-1 levels were significantly increased as compared to sham-operated animals. Treatment with 20 μg/kg rhMFG-E8 significantly reduced these levels. With higher doses, further reductions in AST and ALT (59-62%), creatinine (65-68%), and lactate (46-57%), and serum IL-6 and TNF-α were obtained. The 160 μg/kg dose produced the greatest reduction in serum TNF-α. With treatment with 20 μg/kg rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham values. In a 10-day survival study, vehicle-treated animals produced a 36% survival rate, while rhMFG-E8 significantly improved the survival rate to 68-72%. Treatment with increasing doses of rhMFG-E8 significantly reduced the number of apoptotic cells detected and markedly attenuated the tissue damages observed in the lungs. CONCLUSIONS: These data suggest that recombinant human MFG-E8 is beneficial in ameliorating sepsis in an animal model of sepsis.
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Authors | Kavin G Shah, Rongqian Wu, Asha Jacob, Ernesto P Molmenti, Jeffrey Nicastro, Gene F Coppa, Ping Wang |
Journal | Intensive care medicine
(Intensive Care Med)
Vol. 38
Issue 1
Pg. 128-36
(Jan 2012)
ISSN: 1432-1238 [Electronic] United States |
PMID | 21946914
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, Surface
- Biomarkers
- Glycolipids
- Glycoproteins
- HMGB1 Protein
- Interleukin-6
- Mfge8 protein, mouse
- Milk Proteins
- Recombinant Proteins
- Tumor Necrosis Factor-alpha
- milk fat globule
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Topics |
- Animals
- Antigens, Surface
(administration & dosage, pharmacology, therapeutic use)
- Biomarkers
(blood)
- Dose-Response Relationship, Drug
- Glycolipids
(therapeutic use)
- Glycoproteins
(therapeutic use)
- HMGB1 Protein
(drug effects)
- Humans
- Interleukin-6
(metabolism)
- Lipid Droplets
- Male
- Milk Proteins
(administration & dosage, pharmacology, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Recombinant Proteins
(therapeutic use)
- Sepsis
(drug therapy, pathology)
- Survival Analysis
- Tumor Necrosis Factor-alpha
(drug effects)
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