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[Effect of erythromycin on neutrophil function in chronic respiratory tract diseases with Pseudomonas infection]
1Second Department of Internal Medicine, Nagasaki University School of Medicine.
Abstract:
The "low dose and long term" erythromycin (EM) therapy has been reported as effective (or useful) in chronic respiratory tract disease with pseudomonas (P.) infection including diffuse panbronchiolitis (DPB), however the mode of action is still obscure. Therefore in this study we have examined the effect of EM on the interaction between P. aeruginosa and human polymorphonuclear leukocyte (PMN) in vitro. The efficiency of intracellular killing and the ability of superoxide production were employed to evaluate the PMN functions. For the first step, the following results were obtained; 1) Pretreatment of PMN with 20 micrograms/ml EM did not affect the killing ability of PMNs against opsonized P. aeruginosa of standard and clinical isolate from DPB patient. 2) Superoxide production from PMNs was observed by phagocytosis of P. aeruginosa in the presence of serum. This was not affected by exposure of PMNs to 20 micrograms/ml EM even with increased ratios of bacteria to cells. 3) Pretreatment of P. aeruginosa with 20 micrograms/ml EM before opsonization enhanced the killing ability of PMNs in both standard and clinical isolate. 4) Pretreatment of P. aeruginosa with 20 micrograms/ml EM resulted in no effect on superoxide production from PMNs by phagocytosis of the bacteria. These results indicate that EM may modify a certain step of the interaction between bacteria and intracellular host defence mechanisms. Therefore for the second step, we have investigated the susceptibility of EM-exposed bacteria to killing by the cell free (glucose oxidase-glucose) system, which will detect the enzymatic generation of hydrogen peroxide (H2O2). The following results were observed; 1) EM-exposed bacteria was more susceptible to killing than control bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Low-dose, long-term erythromycin (EM) therapy may improve chronic respiratory infections. This study found EM enhances bacterial susceptibility to immune cells and hydrogen peroxide, suggesting a novel mechanism for its effectiveness in treating Pseudomonas aeruginosa infections.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Context:
- Chronic respiratory tract infections, particularly those involving Pseudomonas aeruginosa and diffuse panbronchiolitis (DPB), often benefit from long-term, low-dose erythromycin (EM) therapy.
- The precise mechanism by which EM exerts its therapeutic effects in these conditions remains incompletely understood.
- Understanding EM's impact on host-pathogen interactions is crucial for optimizing treatment strategies.
Purpose:
- To investigate the in vitro effects of erythromycin (EM) on the interaction between Pseudomonas aeruginosa and human polymorphonuclear leukocytes (PMNs).
- To evaluate how EM influences PMN functions, including intracellular killing and superoxide production.
- To explore potential mechanisms underlying EM's efficacy in chronic respiratory infections.
Summary:
- Pretreatment of PMNs with EM did not alter their killing capacity or superoxide production against P. aeruginosa.
- Pretreatment of P. aeruginosa with EM enhanced its susceptibility to PMN-mediated killing.
- EM-exposed bacteria demonstrated increased susceptibility to killing by a cell-free hydrogen peroxide-generating system.
Impact:
- Erythromycin may exert its beneficial effects by modifying bacterial properties, making them more vulnerable to host defense mechanisms.
- These findings suggest that EM could enhance bacterial susceptibility to oxidative stress, contributing to its efficacy in chronic P. aeruginosa infections.
- This research provides insights into the immunomodulatory and antimicrobial actions of erythromycin, potentially leading to improved therapeutic approaches for respiratory diseases.