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Published on: November 1, 2013
Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro
1Department of Otolaryngology, School of Medicine, Showa University, Tokyo, Japan.
Background:
Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood.
Aim:
The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell.
Methods:
Mast cells were induced by long-term culture of splenocytes from BALB/c mice. RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one. The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day. We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion.
Results And Conclusion:
RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods. RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations. However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml. These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases.
Insights
Roxithromycin (RXM) did not affect mast cell growth or histamine release. However, RXM suppressed inflammatory cytokine secretion, suggesting a mechanism for macrolide antibiotics in treating chronic inflammatory diseases.
Area of Science:
- Immunology
- Pharmacology
Background:
- Macrolide antibiotics can improve inflammatory diseases like cystic fibrosis.
- Mechanisms of macrolide benefits in inflammatory conditions are not fully understood.
Purpose of the Study:
- To investigate the effect of roxithromycin (RXM) on mast cell functions.
- To explore macrolide antibiotic influence on effector cells in inflammation.
Main Methods:
- Mast cells were cultured from mouse splenocytes.
- Roxithromycin (RXM) was administered during mast cell culture.
- Mast cell growth, histamine release, and cytokine secretion were assessed.
Main Results:
- RXM did not inhibit mast cell growth.
- RXM did not suppress histamine release upon stimulation.
- RXM significantly reduced inflammatory cytokine (IL-1β, IL-6, GM-CSF, TNF-α) secretion.
Conclusions:
- RXM modulates mast cell inflammatory cytokine production.
- This cytokine suppression may explain the clinical benefits of macrolides in chronic inflammatory diseases.
