Abstract |
The potency of clarithromycin as immunomodulator was assessed in an experimental model of sepsis based on acute pyelonephritis by susceptible Escherichia coli. 55 rabbits were utilized; 5 for preliminary pharmacokinetic study and 50 for treatment. The latter were divided into 5 groups of treatment, A: controls; B: clarithromycin pretreatment; C: amikacin pretreatment; D: clarithromycin treatment on presentation of pulmonary oedema; and E; amikacin treatment on presentation of pulmonary oedema. Survival was recorded; tumour necrosis factor-alpha ( TNFalpha), and malondialdehyde (MDA) were estimated in serum; activities of caspase-3 in monocyte cytosolic extracts were studied; and bacterial counts made in various organs. Median survival of animals of groups A, B, C, D and E was 1.0, 21.0, 12.5, 2.0 and 5.0 d, respectively. TNFalpha and MDA and monocyte caspase-3 activity of group A increased over time; no increases were detected in groups B and C. Concentrations of MDA and activities of monocytic caspase-3 were decreased after administration of clarithromycin in group D, an effect not occurring in group E. Bacterial load was decreased in renal tissue of group D compared to group A. It is concluded that intravenous clarithromycin might constitute a promising immunomodulator in sepsis even in the advent of pulmonary oedema.
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Authors | Evangelos Giamarellos-Bourboulis, Theodoros Adamis, Lambros Sabracos, Maria Raftogiannis, Fotini Baziaka, Thomas Tsaganos, Pantelis Koutoukas, Diamantis Plachouras, Panayotis Karayannacos, Helen Giamarellou |
Journal | Scandinavian journal of infectious diseases
(Scand J Infect Dis)
Vol. 37
Issue 1
Pg. 48-54
( 2005)
ISSN: 0036-5548 [Print] England |
PMID | 15764190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Immunologic Factors
- Tumor Necrosis Factor-alpha
- Malondialdehyde
- Amikacin
- Caspase 3
- Caspases
- Clarithromycin
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Topics |
- Acute Disease
- Amikacin
(therapeutic use)
- Animals
- Anti-Bacterial Agents
(blood, pharmacokinetics, therapeutic use)
- Caspase 3
- Caspases
(metabolism)
- Clarithromycin
(blood, pharmacokinetics, therapeutic use)
- Colony Count, Microbial
- Escherichia coli
(isolation & purification, pathogenicity)
- Escherichia coli Infections
(drug therapy, metabolism)
- Immunologic Factors
(blood, therapeutic use)
- Male
- Malondialdehyde
(blood)
- Pulmonary Edema
(drug therapy)
- Pyelonephritis
(drug therapy, metabolism)
- Rabbits
- Sepsis
(drug therapy, metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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