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Abnormal neutrophil chemotaxis and random migration induced by aminoglycoside antibiotics
Abstract:
Gentamicin and amikacin, administered in therapeutic doses to normal healthy adults, caused a transient decrease in chemotactic migration of their PMNs. In contrast, RM of leukocytes obtained from these individuals was increased significantly. The magnitude of these changes did not correlate with the serum antibiotic concentrations. Separate in vitro experiments with gentamicin, however, revealed an inverse dose-response relationship with chemotactic suppression. The mechanism(s) involved in modifications of these leukocyte functions is not well understood. These findings may be of clinical significance in patients, especially those with altered host defense mechanisms, who require therapy with these aminoglycoside antimicrobial agents.
Insights
Therapeutic doses of gentamicin and amikacin temporarily reduced neutrophil migration but increased leukocyte random migration in healthy adults. These antibiotic effects on immune cells may impact patients with compromised defenses.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Aminoglycoside antibiotics like gentamicin and amikacin are widely used to treat bacterial infections.
- Leukocyte functions, including migration, are crucial components of the host defense system.
- The impact of therapeutic aminoglycoside doses on polymorphonuclear neutrophils (PMNs) and overall leukocyte function requires further elucidation.
Purpose of the Study:
- To investigate the effects of gentamicin and amikacin on polymorphonuclear neutrophil (PMN) chemotaxis and random migration (RM) in healthy adults.
- To explore the relationship between serum antibiotic concentrations and observed changes in leukocyte function.
- To examine the in vitro dose-response relationship of gentamicin on PMN chemotaxis.
Main Methods:
- Healthy adult volunteers received therapeutic doses of gentamicin or amikacin.
- Leukocyte functions, specifically PMN chemotaxis and RM, were assessed.
- Serum antibiotic concentrations were measured.
- In vitro experiments were conducted to evaluate gentamicin's effect on PMN chemotaxis in a dose-dependent manner.
Main Results:
- In vivo administration of gentamicin and amikacin led to a transient decrease in PMN chemotactic migration.
- Simultaneously, random migration (RM) of leukocytes from these individuals significantly increased.
- No direct correlation was observed between the magnitude of these functional changes and serum antibiotic concentrations.
- In vitro studies demonstrated an inverse dose-response relationship between gentamicin concentration and PMN chemotactic suppression.
Conclusions:
- Gentamicin and amikacin can transiently alter key leukocyte functions, specifically decreasing PMN chemotaxis and increasing RM in healthy adults.
- The observed effects do not appear to be directly correlated with serum antibiotic levels in vivo.
- An in vitro inverse dose-response relationship suggests direct effects of gentamicin on PMN chemotaxis.
- These findings may have clinical implications for patients with compromised immune systems undergoing aminoglycoside therapy.