The Use of Antimicrobial Agents for Noninfectious Diseases

Berger, Stephen A.

doi:10.1093/clinids/7.3.357

Cited by 15 publications

(1 citation statement)

References 113 publications

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“…Figure 4 shows the effects of pretreatment with macrolide antibiotics (EM, CAM, RXM, and AZM) on macrophage cytocidal activity against Candida albi- Antibiotics have biological properties other than direct antimicrobial activity. These include interactions with and alteration in the functions of host phagocytic cells (4,13,15,28). This subject is of importance, since phagocytic cells are essential for controlling almost all infections and are mediators of inflammation.…”

Section: Methodsmentioning

confidence: 99%

Effect of Macrolide Antibiotics on Macrophage Functions

Fujita

Negayama

et al. 1996

Microbiology and Immunology

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Macrolide antibiotics have a variety of actions other than antimicrobial activities. Recently, it has been suggested that macrolide antibiotics act as immunomodulators.In this study, we evaluated the effects of macrolide antibiotics on macrophage functions.For the macrophage, we used the mouse macrophage cell line J774.1. The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage. In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans. These results suggest that macrolide antibiotics stimulate macrophage functions. There is increasing evidence that long-term administration of the macrolide antibiotic erythromycin (EM) is effective in the treatment of chronic respiratory infections, probably through actions other than its antimicrobial properties (19). Although the mechanism of the efficacy is uncertain, several hypotheses have been proposed, such as the immunomodulatory action of macrolide antibiotics. Macrolide antibiotics modulate the functions of inflammatory cells such as polymorphonuclear leukocytes, lymphocytes and macrophages (1, 33). In addition, macrolide antibiotics directly affect airway secretory cell (12) and epithelial cell (35) functions. These effects are proposed to explain the efficacy of macrolides in the treatment of inflammatory airway diseases. Several studies have been conducted concerning the interaction between phagocytic cells and macrolide antibiotics. However, there are few reports that evaluate the interaction between macrophage functions and several macrolide antibiotics. With this background, we evaluated various aspects of the interaction between four macrolide antibiotics and macrophages. These studies included the effect on growth, effect on phagocytic activity, effect on chemotaxis to lipopolysaccharide (LPS), and effect of cytotoxicity against Candida albicans. Materials and MethodsMacrophage. We used a murine macrophage cell line, J774.1. This cell line was obtained from the RIKEN Cell Bank (Ibaraki, Japan). This cell line was cultured in RPMI-1640 medium with 10% fetal bovine serum (FBS).Antibiotics. The EM (Japan Dynabot Co., Tokyo), clarithromycin (CAM, Japan Dynabot Co.), roxithromycin (RXM, Roussel Uclaf, Paris, France), and azithromycin (AZM, Pfizer Pharmaceuticals Inc., Japan) were provided by the respective manufacturers. These 4 drugs were dissolved in 90% methanol at a concentration of 2 mg/ml as a stock solution; then diluted with RPMI-1640 medium with 10% FBS. Several final concentrations of macrolide antibiotics (4 concentrations of each antibiotic) were used in the following experimen...

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Section: Methodsmentioning

confidence: 99%