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Published on: December 30, 2014
Meropenem: effects on human leukocyte functions and interleukin release
G Matera1, M C Berlinghieri, A Focà
1Institute of Microbiology, Policlinico Mater Domini, University of Reggio Calabria, Catanzaro, Via T. Campanella, 88100 Catanzaro, Italy.
Abstract:
Modifications of the immune response have been reported for a number of antimicrobial agents following both in vivo and in vitro experiments. Present results were obtained from in vitro incubated human polymorphonuclear cells (PMN) and monocytes treated with meropenem, a novel carbapenem antibiotic. Only the highest concentrations of meropenem (50-200 microg/ml) significantly reduced the phagocytic activity and unstimulated superoxide release of neutrophils after 1 h of incubation. Moreover meropenem (100 and 200 microg/ml) reduced PMA-stimulated superoxide release by PMN after 1 h of incubation. Only the highest concentration used (200 microg/ml) was found to reduce significantly superoxide release by PMA-unstimulated and -stimulated PMN incubated for 2 h. Meropenem did not affect some of the PMN functions studied (killing of Candida albicans, chemotaxis and glucose consumption) over a broad range of concentrations (5, 10, 20, 50, 100, 200 microg/ml). The leukocyte viability did not change even at the highest antibiotic concentration used, as showed by the trypan blue exclusion test. The LPS-induced release of IL-1alpha, IL-6 and IL-8 from isolated monocytes was not impaired by meropenem (100 and 200 microg/ml), that significantly reduced TNFalpha stimulated by LPS, after 4 h of incubation. In conclusion our data suggest that therapeutically relevant concentrations (5-20 microg/ml) of meropenem did not modify substantially the viability and the functions of human leukocytes.
Insights
Therapeutically relevant concentrations of meropenem, a carbapenem antibiotic, show minimal impact on human leukocyte viability and function. High concentrations may affect neutrophil superoxide release but not essential immune responses.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Antimicrobial agents can modulate immune responses.
- Meropenem is a novel carbapenem antibiotic with broad-spectrum activity.
Purpose of the Study:
- To investigate the in vitro effects of meropenem on human polymorphonuclear cells (PMN) and monocytes.
- To assess meropenem's impact on leukocyte viability and immune functions.
Main Methods:
- In vitro incubation of human PMN and monocytes with varying meropenem concentrations.
- Assays for phagocytic activity, superoxide release, Candida albicans killing, chemotaxis, glucose consumption, and cytokine release (IL-1α, IL-6, IL-8, TNF-α).
- Trypan blue exclusion test for leukocyte viability.
Main Results:
- High meropenem concentrations (50-200 μg/ml) reduced neutrophil phagocytosis and superoxide release after 1-2 hours.
- Meropenem did not affect PMN functions like Candida killing, chemotaxis, or glucose consumption.
- Monocyte release of IL-1α, IL-6, and IL-8 was not impaired, but TNF-α release was reduced at higher concentrations.
- Leukocyte viability remained unaffected even at the highest tested concentrations.
Conclusions:
- Therapeutically relevant concentrations (5-20 μg/ml) of meropenem do not substantially alter human leukocyte viability or function.
- Meropenem exhibits minimal immunomodulatory effects at concentrations typically used in clinical settings.
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