Effect of Macrolide Antibiotics on Macrophage Functions

Abstract

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...

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

“…Nevertheless, its action mechanism is still unknown and it might be related to leishmanicide direct effect and/or immunomodulatory action (XU et al, 1996;IANARO et al, 2000).…”

Activity of azithromycin against Leishmania major in vitro and in vivo.

“…35 In addition, effects on macrophage functions include stimulation of phagocytosis, chemotaxis, and cytocidal activity. 31 On this basis, it has been suggested that the ability of azithromycin to accumulate in the tissues and especially in phagocytes can act synergistically with the host immune system. 36 It is possible that azithromycin in mice infected with L. major enhances the immune response, but this effect is patent only when the inherent immune response is suboptimal.…”

“…Alternatively, azithromycin has been shown to enhance the ability of macrophages to eliminate many different pathogens. [29][30][31] Macrophage activation might be the killing mechanism induced with azithromycin against amastigotes in macrophages. It is also possible that azithromycin has a direct killing effect and an immunomodulatory effect.…”

Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages

“…In addition, a few studies have reported increased macrophage phagocytic activity in the presence of these antibiotics (using neutrophils or beads as targets) [7,8]. However, the effect of macrolide antibiotics on phagocytosis of apoptotic bronchial epithelial cells by AMs, particularly with regard to COPD, has not been studied previously.…”