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Enhanced neutrophil function in children on bromide therapy
R W Steele1, R C Woody, R W Steele
1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Insights
Bromide therapy in children enhances neutrophil function, boosting bacterial killing. Higher bromide levels initially increase, then decrease, this immune response, suggesting a therapeutic window for optimal host defense.
Area of Science:
- Immunology
- Pharmacology
Background:
- Neutrophil bacterial killing involves toxic halide complex formation.
- Bromide (Br-) is used in anticonvulsant therapy.
Purpose of the Study:
- To investigate neutrophil function in children undergoing bromide therapy.
- To determine the relationship between serum bromide concentrations and neutrophil activity.
Main Methods:
- Collected whole blood and serum from 7 patients on bromide elixir.
- Measured neutrophil function using luminol-enhanced chemiluminescence (CL).
- Determined serum bromide concentrations ([Br-]).
Main Results:
- A direct correlation (r=0.87) was observed between [Br-] and neutrophil CL activity.
- Peak CL responses were higher than controls within the therapeutic [Br-] range (10-20 mM).
- In vitro addition of Br- to control neutrophils dose-dependently enhanced CL activity, with optimal enhancement at 30 mM.
Conclusions:
- Bromide ions enhance neutrophil phagocytic and bactericidal activity.
- Bromide therapy may potentially augment host defense capabilities against bacterial infections.
Abstract:
The final step in neutrophil bacterial killing is formation of a toxic halide complex. For this reason, we studied neutrophil function in children receiving bromide anticonvulsant therapy. Whole blood and serum were obtained from 7 patients with seizure disorders treated orally with triple bromide elixir to examine neutrophil function as measured by luminol enhanced chemiluminescence (CL). Serum bromide concentrations [Br-] were determined concomitantly. There was a direct correlation between [Br-] and CL activity of neutrophils (r = 0.87) with peak CL responses significantly higher than controls when [Br-] were in the therapeutic range (10-20 mM). With [Br-] above 25 mM, CL activity was reduced. Serum from patients also enhanced CL of control neutrophils with a similar relationship to measured [Br-]. To confirm that enhanced neutrophil activity was attributable to [Br-] use, [Br-] ranging from 0-50 mM were added to control neutrophils in otherwise normal physiologic conditions and the CL assay was performed. Results expressed as percent of control values were as follows: [Br-] 5 mM, 110%; 10 mM, 158%; 15 mM, 194%; 20 mM, 252%; 25 mM, 136%; 30 mM, 364%; and 50 mM, 205%. These data demonstrate that Br- enhances phagocytic and bactericidal activity of neutrophils and suggest that Br- therapy may augment host defense capabilities.