Spiramycin uptake by alveolar macrophages

Harf, R; Panteix, G.; Desnottes, J. F.; Diallo, N.; Leclercq, M.

doi:10.1093/jac/22.supplement_b.135

Cited by 18 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…**, P < 0.01; *, P < 0.05. of antibiotics taken up and concentrated by leukocytes; as a result, they can reach intracellular concentrations far higher than those attained in the extracellular medium (8,21,28). Furthermore, their different pharmacokinetic properties, especially with respect to their biological half-lives and intracellular concentrations at a given time (9,16,27,28), could explain their differential effects on IL-6 production within the same group. Indeed, differences in their interactions with phagocytes have already been shown (24,32).…”

Section: Resultsmentioning

confidence: 99%

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Bailly

Pocidalo

Fay

et al. 1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Antibiotics do not act alone but act in conjunction with the host defense system. In pairticular, it has been shown that some antibiotics can modify cytokine production. We compared the in vitro effiects of three macrolides (roxithroinycin, spiramycin, and erythromycin) actively concentrated by leukocytes on interleukinla, (IL-la), IL-1p, , and tumor necrosis factor alpha. production by human monocytes stimulated with lipopolysaccharide. Our results show that the three macrolides tested have different effects on production of these cytokines. Spiramycin and, to a lesser extent, erythromycin increased total IL-6 production without affecting IL-la, IL-1j0, or tumor necrosis factor alpha production, whereas roxithromycin had no effect. To our knowledge, this is the first time that an antibiotic has been shown to increase IL-6 production.Over the last 20 years, a growing interest in the study of interactions between antimicrobial agents and host defense systems has arisen. In effect, a wide range of antimicrobial agents administered in vivo or in vitro have been reported to modify host immune responses (14,17,31), including cytokine production (3,4,20,29,30).Interleukin-la (IL-la), and IL-1p, IL-6, and tumor necrosis factor alpha (TNF-a) are the major cytokines produced by mononuclear phagocytes (6, 10, 23, 34). They mediate a wide range of biological activities that play a critical role in the induction of inflammatory and immune responses. Although these cytokines are biochemically and immunologically distinct proteins transcribed from different genes, they share a number of activities, such as the induction of fever and acute-phase protein synthesis by the liver (5,12,15,26). They have also been found to exhibit synergy, and each can modulate the production of the others (1,25,33).Macrolides are a class of antibiotics taken up and concentrated by leukocytes; as a result, they can reach intracellular concentrations far higher than those attained in the extracellular medium (8,21,28 Cytokine production. Following adherence, the cells were washed, and 1 ml of fresh serum-free medium was added to the monolayers with 10 p,g of lipopolysaccharide (LPS) (Escherichia coli O.55:B5; Difco) per ml and with or without various concentrations of the antibiotics (1, 10, and 50 ,ug/ml). Cultures were incubated for 18 h at 37°C in a humidified atmosphere of 95% air and 5% CO2. To determine extracellular cytokine concentrations, cell-free supernatants were collected, centrifuged at 800 x g for 10 min, and stored at -70°C until assay. To determine cell-associated cytokine concentrations, the cells remaining in the wells were covered with 1 ml of fresh medium, lysed with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate (CHAPS) (9 mM; Sigma) for 30 min, and stored at -70°C until assay. Addition of CHAPS to any of the recombinant cytokines used in this experiment did not modify the immunoassays.

show abstract

Section: Resultsmentioning

confidence: 99%

Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin

Bailly

Pocidalo

Fay

et al. 1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In cases of lower respiratory tract infections, chemical analysis of sputum (6,9,28) and analyses of tissue biopsy specimens and bronchoalveolar lavage fluid (15,32), epithelial lining fluid (4,35), and alveolar macrophages (12,13) have been performed to obtain information about the penetration of antibiotics into the lungs (3,16). However, the determination of concentrations of antibiotics in sputum is unreliable.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of antibiotics have been measured in sputum samples (6,9,19,28), bronchoscopically harvested biopsy specimens, and bronchoalveolar lavage fluids (15,32). More sophisticated approaches include the determination of antibiotic concentrations in epithelial lining fluid (4,35) or in alveolar macrophages (12,13). Recently, imaging procedures such as planar gamma scintigraphy (21) and positron emission tomography (39) were applied to support the definition of optimal dosing schedules for respiratory tract infections.…”

mentioning

confidence: 99%

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

Tomaselli

Maier

Matzi

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values.

show abstract

“…Prior to measuring antimicrobial agent concentrations in AMs, the in vitro efflux characteristics must be examined, and it must be ensured that significant efflux does not occur during the BAL procedure. This important validation step has not been taken for most studies (10,23,46). Only two of the published studies of antimicrobial agent concentrations in human AMs in vivo have addressed this problem, and these studies examined azithromycin, which has been shown to efflux from phagocytes very slowly (5,17), so that significant efflux during BAL is unlikely.…”

Section: Introductionmentioning

confidence: 99%