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Effects of enrofloxacin on porcine phagocytic function
E J Schoevers1, L A van Leengoed, J H Verheijden
1Department of Herd Health and Reproduction, University of Utrecht, Utrecht, The Netherlands.
Abstract:
The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 microg/ml. Enrofloxacin (0.5 microg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5x the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida, and similar intra- and extracellular reductions of P. multocida isolates by enrofloxacin were found. Intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin at 5x the MIC in both PMNs and AMs. AMs are very susceptible to the A. pleuropneumoniae cytotoxin. This suggests that in serologically naive pigs the enhancing effect of enrofloxacin on the bactericidal action of PMNs may have clinical relevance.
Insights
Enrofloxacin accumulates in porcine phagocytes, enhancing bacterial killing, particularly for Actinobacillus pleuropneumoniae. This suggests a potential clinical benefit in treating infections in pigs.
Area of Science:
- Veterinary Pharmacology
- Immunology
- Antimicrobial Resistance
Background:
- Enrofloxacin is a fluoroquinolone antibiotic commonly used in veterinary medicine.
- Phagocytes play a crucial role in the innate immune response against bacterial infections in pigs.
- Understanding enrofloxacin's interaction with phagocytes is essential for optimizing its therapeutic efficacy.
Purpose of the Study:
- To investigate the interaction between enrofloxacin and porcine phagocytes (polymorphonuclear leukocytes and alveolar macrophages).
- To evaluate the effect of enrofloxacin on phagocyte function, including uptake, intracellular killing, and viability.
- To assess the clinical relevance of enrofloxacin's effects on phagocytes in the context of common swine pathogens.
Main Methods:
- Culturing porcine polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs).
- Treating phagocytes with clinically relevant concentrations of enrofloxacin.
- Quantifying enrofloxacin accumulation within cells using cellular/extracellular concentration ratios.
- Assessing phagocyte viability, chemotaxis, phagocytosis of microparticles and bacteria (Actinobacillus pleuropneumoniae, Pasteurella multocida, Staphylococcus aureus), and intracellular killing.
- Measuring bacterial reduction in the presence and absence of enrofloxacin.
Main Results:
- Enrofloxacin accumulated significantly in both PMNs (ratio 9) and AMs (ratio 5).
- Phagocytes released 80-90% of accumulated enrofloxacin within 10 minutes in drug-free medium.
- Enrofloxacin did not affect phagocyte viability or PMN chemotaxis at tested concentrations.
- Enrofloxacin enhanced the intracellular killing of Actinobacillus pleuropneumoniae by both PMNs and AMs at 5x the minimum inhibitory concentration (MIC).
- PMNs effectively killed Staphylococcus aureus with or without enrofloxacin, while AMs showed reduced intracellular killing of S. aureus.
- Enrofloxacin demonstrated similar intra- and extracellular reductions for Pasteurella multocida, which was not effectively phagocytosed by PMNs.
Conclusions:
- Enrofloxacin exhibits significant intracellular accumulation in porcine phagocytes.
- Enrofloxacin enhances the intraphagocytic killing of Actinobacillus pleuropneumoniae, suggesting potential clinical benefits.
- The study highlights the importance of considering enrofloxacin's immunomodulatory effects on phagocytes for effective treatment strategies in swine bacterial infections.