Effects of Clarithromycin on Inflammatory Cell Mediator Release and Survival

Abstract

Background: Clarithromycin exhibits anti-inflammatory as well as antimicrobial activity, leading to decreased symptoms of asthma and chronic sinusitis. The mode of anti-inflammatory effects of clarithromycin on inflammatory cells is not well understood. We hypothesized that clarithromycin inhibits inflammatory cell mediator release and survival. Methods: We investigated the effects of this drug on survival and mediator release from mast cells, eosinophils and neutrophils. Results: Human eosinophil and neutrophil respiratory burst was inhibited by up to 54% after 1–2 h pretreatment with 100 µg/ml clarithromycin. Similar doses of erythromycin did not affect respiratory burst responses in these cells. Clarithromycin at doses of up to 100 µg/ml had no effect on granule-derived mediators released from mast cells and neutrophils. However, we found that clarithromycin (100 µg/ml) induced cell death in mast cells and eosinophils after 16–48 h incubation. Conclusion: Clarithromycin inhibited inflammatory cell mediator release and survival, which may enhance its ability to reduce the symptoms of chronic sinusitis and asthma.

Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from β-defensin 2-stimulated mast cells

“…A few experiments reported on the effect of macrolides on mast cell function. Clarithromycin was demonstrated to induce cell death in mast cells (23). In contrast to the present study, Shimane et al (24) reported that RXM (~100 μg/ml) did not inhibit histamine release from mouse mast cells stimulated by chemical substances (compound 48/80 and calcium ionophore A23187) and immunologic stimulants using mouse IgE and anti-mouse IgE.…”

Evaluation of Different Compounds as Quorum Sensing Inhibitors inPseudomonas aeruginosa

“…It has been demonstrated that various analogues of S-adenosylmethionine, such as ceftazidime and tobramycin, are strong inhibitors of AHL synthesis [19][20][21] . Some macrolides, although inactive on P. aeruginosa by conventional standards, block AHL 22 , exhibit anti-inflammatory activity 23 and suppress virulence factor production and biofilm formation [24][25][26] . Garlic, renowned for its anti-fungal, anti-cancer and antimicrobial activities related to the presence of allicin and derivatives 27,28 , also demonstrated QSI properties 15,29 .…”

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

“…With this dose, the physiological concentration of clarithromycin in the serum was around 3 μ M at peak levels and less than 1 μ M at trough levels [24], while it ranged between 10 and 15 μ M in lung tissues [25]. However, in in vitro studies using mast cells, eosinophils, and neutrophils, clarithromycin doses as high as 100 μ M were required to effectively elicit its inhibitory effect on the release of chemical mediators [13]. Therefore, we tried doses starting at 1 μ M up to 100 μ M in the present study (fig.…”

“…By measuring the amount of chemical mediators, e.g. histamine or β-hexosaminidase, released from mast cells, previous studies have tried to determine the effects of macrolide antibiotics on the stabilization of mast cells [12,13,14,15]. However, due to the limitations of the methods used in molecular biology [16], the effects of these drugs on the exocytotic process could not directly been examined in mast cells.…”