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Updated: Jul 20, 2026
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa
Evangelos J Giamarellos-Bourboulis1, Taxiarchis Geladopoulos, Michael Chrisofos
1Fourth Department of Internal Medicine, Medical School, University of Athens, Greece. giamarel@ath.forthnet.gr
Abstract:
Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines.
Insights
Oleuropein, an olive tree compound, shows promise in treating sepsis. It improved survival rates and reduced bacterial load in experimental models, suggesting it enhances immune response.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Sepsis is a life-threatening condition often caused by bacterial infections.
- Pseudomonas aeruginosa is a common pathogen associated with sepsis.
- Novel immunomodulators are needed to combat antibiotic-resistant bacteria.
Purpose of the Study:
- To evaluate the immunomodulatory and therapeutic effects of oleuropein in experimental sepsis.
- To assess oleuropein's efficacy against multidrug-resistant Pseudomonas aeruginosa.
- To investigate oleuropein's impact on inflammatory markers and survival rates.
Main Methods:
- In vitro studies using monocyte and neutrophil cultures exposed to lipopolysaccharide (LPS) and P. aeruginosa.
- In vivo experimental sepsis induced by P. aeruginosa in rabbits.
- Treatment groups included oleuropein, amikacin, and combination therapy.
- Measurements included bacterial counts, inflammatory cytokines (TNF-alpha, IL-6), malondialdehyde, and total antioxidant status.
Main Results:
- Oleuropein reduced P. aeruginosa counts in monocyte cultures.
- Median survival was significantly prolonged in rabbits treated with oleuropein (alone or with amikacin) compared to controls.
- Bacterial load in blood and organs was reduced by oleuropein treatment.
- Oleuropein treatment maintained total antioxidant status and reduced TNF-alpha levels.
Conclusions:
- Oleuropein demonstrates significant therapeutic potential in experimental sepsis.
- Its mechanism may involve enhanced phagocytosis and inhibition of pro-inflammatory cytokine production.
- Oleuropein offers a promising alternative or adjunct therapy, particularly against resistant bacterial strains.
