Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa.
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.
Giamarellos-Bourboulis
Evangelos J
EJ
Fourth Department of Internal Medicine, Medical School, University of Athens, Greece. giamarel@ath.forthnet.gr
Geladopoulos
Taxiarchis
T
Chrisofos
Michael
M
Koutoukas
Pantelis
P
Vassiliadis
John
J
Alexandrou
Ioannis
I
Tsaganos
Thomas
T
Sabracos
Labros
L
Karagianni
Vassiliki
V
Pelekanou
Emilia
E
Tzepi
Ira
I
Kranidioti
Hariklia
H
Koussoulas
Vassilios
V
Giamarellou
Helen
H
D000583:Amikacin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D057888:Iridoid Glucosides; D039823:Iridoids; D008297:Male; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality; D011550:Pseudomonas aeruginosa; D011714:Pyrans / Q000494:pharmacology*; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013534:Survival / Q000502:physiology / Q000523:psychology*
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D007155:Immunologic Factors; D057888:Iridoid Glucosides; D039823:Iridoids; D011714:Pyrans; C002769:oleuropein; D000583:Amikacin