Effect of Clarithromycin on Macrophage Functions

Abstract

Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effect of clarithromycin (CAM) on macrophage function. We used the mouse macrophage cell line, J774.1. The following direct effects of CAM on macrophage function were evaluated: chemotaxis to CAM, chemokinetic effect of CAM, and the effect of CAM on macrophage growth. In order to examine the indirect effects of CAM on macrophage functions, we preincubated macrophages with several concentrations of CAM and then removed the CAM. Thereafter, the phagocytosis of beads, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide were evaluated. In addition, the indirect effects of CAM on endoxan (4 mg/ml) treated macrophage phagocytosis, cytocidal activity, and chemotaxis were evaluated. CAM (at the concentration between 0.04 and 0.2 microgram/ml) directly stimulated macrophage chemotaxis and chemokinesis. In addition, CAM dose-dependently stimulated the growth of macrophages. CAM pretreatment (for 4 hours at the concentrations between 0.04 and 0.2 microgram/ml) stimulated macrophage phagocytosis, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide. In addition, CAM recovered macrophage phagocytosis, cytocidal activity, and chemotaxis which were decreased after endoxan exposure. These results suggest that CAM has direct and indirect effects on macrophage functions.

WBC count and functional changes induced by co-administration of clofazimine and clarithromycin, in single and multiple doses, in Wistar rats

“…The literature is controversial regarding the action of clarithromycin on the neutrophilic phagocytosis. While a report observed a decreased phagocytosis associated to the drug (Wenisch et al, 1996), other studies reported an increased activity (Roszkowski et al, 1990;Scaglione et al, 1993;Xu et al, 1995). Differences in methodology, the animal and human models used, the concentrations of the drug in vivo and in vitro, the protocols, and dosage and administration may partially explain the differences reported by these studies (Labro, 2000).…”

Clarithromycin Inhibits the Development of Dermatitis in NC/Nga Mice

“…The remaining MHC class II-positive cells were probably macrophages, based on their morphology [11]. It has been reported that CAM directly stimulates macrophage functions, such as phagocytosis, which were decreased after endotoxin exposure [25]. The number of dermal macrophages and mast cells in dexamethasonetreated mice was numerous at 9 weeks, which may be due to the particularly low sensitivity to steroids [11].…”

Evaluation of the Immunomodulatory Effects of the Macrolide Antibiotic, Clarithromycin, in Female B6c3f1 Mice: A 28-Day Oral Gavage Study

“…Woo et al 20 recently demonstrated that CRTM suppressed both the systemic and local inflammatory response following surgical trauma, in part, by suppressing monocytosis. Xu et al 17 on the other hand, reported that CRTM dose-dependently stimulated the growth of J744.1 macrophages, in addition to increasing their phagocytic, chemotactic, and cytolytic activity. Increased monocyte phagocytic activity and intracellular killing has also been demonstrated in human patients that were receiving CRTM therapy to treat chronic bronchitis 4 .…”

“…Murine studies conducted by Takeshita et al 16 showed that CTRM significantly reduced IL-1 production by peritoneal macrophages, IL-1-induced thymocyte proliferation, and the transformation of splenic lymphocytes. More recently, CRTM was reported to enhance macrophage phagocytosis, chemotaxis and cytolytic activity using the murine macrophage cell line, J774.1 17 .…”