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Modulation of human polymorphonuclear neutrophil function by macrolides: preliminary data concerning dirithromycin
M T Labro1, J el Benna, H Abdelghaffar
1Inserm U. 294, Laboratoire d'Immunologie et d'Hématologie CHU X. Bichat, Paris, France.
Abstract:
Polymorphonuclear neutrophils (PMN) play a prominent role in the host response to infectious diseases. One major bactericidal mechanism used by these cells is the production of reactive oxygen species during what is referred to as the oxidative burst. However, excessive oxidant generation can also be involved in cell and tissue damage associated with severe inflammatory reactions. Macrolide antibiotics are able to penetrate and concentrate within phagocytes and have been successfully used to treat infections due to facultative intracellular pathogens. However, intracellular accumulation of macrolides with possible alkalinization of cellular compartments may interfere with normal cell function. In-vitro and ex-vivo data suggest that macrolides affect various phagocytic functions. This paper presents an overview of the published data concerning the modulation of neutrophil function by macrolides. Preliminary data concerning the in-vitro modulation of the neutrophil oxidative burst by dirithromycin and its metabolite, erythromycylamine, are also discussed.
Insights
Macrolide antibiotics impact neutrophil function, including the oxidative burst, which is crucial for fighting infections. This review examines how macrolides affect neutrophils and discusses preliminary data on dirithromycin and erythromycylamine.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Polymorphonuclear neutrophils (PMN) are key in host defense against pathogens.
- The neutrophil oxidative burst produces reactive oxygen species for bacterial killing but can cause tissue damage.
- Macrolides concentrate in phagocytes, potentially altering cellular functions.
Purpose of the Study:
- To review macrolide effects on neutrophil function.
- To discuss macrolide-induced changes in phagocytic activities.
- To present preliminary data on dirithromycin and erythromycylamine's impact on the neutrophil oxidative burst.
Main Methods:
- Literature review of published data on macrolides and neutrophil function.
- In-vitro and ex-vivo experimental data analysis.
- Discussion of preliminary in-vitro modulation of the neutrophil oxidative burst.
Main Results:
- Macrolides are known to affect various phagocytic functions.
- Intracellular accumulation of macrolides may lead to compartment alkalinization, impacting cell function.
- Preliminary data suggest dirithromycin and erythromycylamine modulate the neutrophil oxidative burst.
Conclusions:
- Macrolides can modulate neutrophil function, with implications for treating intracellular pathogens.
- Understanding these effects is crucial for optimizing antibiotic therapy and minimizing host damage.
- Further research on specific macrolides like dirithromycin is warranted.