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[Influence of antibiotics on the production of interleukin-1 by macrophages]
Abstract:
Influence of cefoxitin and cefotaxime on interleukin-1 production (IL-1) by mice peritoneal resident macrophages activated by opsonized zymosan was investigated. Evaluation of the in vivo effect was done by examining macrophages of animals following intravenous administration of 30 mg/kg cefoxitin or cefotaxime. In vitro studies consisted in testing IL-1 production by macrophages in cell cultures in the presence of either antibiotic. In vivo IL-1 production was unchanged following cefoxitin treatment of cell donors, whereas a more than threefold increase was observed after administration of cefotaxime. In vitro, IL-1 production was enhanced by both antibiotics, but the pattern and extent of this effect diverged widely. Cefoxitin in a concentration of 300 micrograms/ml induced a threefold increase in IL-1 production. IL-1 production was increased tenfold and eightfold respectively by 150 and 300 micrograms/ml cefotaxime. When the concentration of either antibiotic was very high (400 micrograms/ml), the effect was significantly less important; a certain degree of inhibition was even observed with cefotaxime. Effects of cefoxitin and cefotaxime on IL-1 production and--as shown in previous studies--on prostaglandin E2 (PGE2) production and sensitivity of immunocompetent cells to PGE2 may be important factors in the mechanism of immunological side effects which result in a modulation of the course of experimental infection.
Insights
Cefotaxime significantly increased interleukin-1 (IL-1) production in mice macrophages in vivo, while cefoxitin did not. Both antibiotics enhanced IL-1 production in vitro, with cefotaxime showing a more potent effect.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Interleukin-1 (IL-1) is a key cytokine in immune responses.
- Macrophage activation by opsonized zymosan is a standard model for studying inflammatory mediators.
- Antibiotic-induced immunomodulation can influence infection outcomes.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of cefoxitin and cefotaxime on IL-1 production by mouse macrophages.
- To compare the immunomodulatory potential of these two cephalosporin antibiotics.
Main Methods:
- In vivo study: Intravenous administration of cefoxitin or cefotaxime (30 mg/kg) to mice, followed by macrophage isolation and IL-1 assessment.
- In vitro study: Macrophages cultured with varying concentrations of cefoxitin or cefotaxime (150-400 µg/ml) in the presence of opsonized zymosan, with subsequent IL-1 measurement.
- IL-1 production was quantified using established assays.
Main Results:
- In vivo: Cefoxitin administration did not alter macrophage IL-1 production, whereas cefotaxime led to a threefold increase.
- In vitro: Both antibiotics enhanced IL-1 production, but cefotaxime demonstrated a dose-dependent enhancement (10-fold at 150 µg/ml, 8-fold at 300 µg/ml).
- High antibiotic concentrations (400 µg/ml) showed reduced effects, with cefotaxime even exhibiting some inhibitory activity.
Conclusions:
- Cefotaxime exhibits significant in vivo immunomodulatory effects on IL-1 production, unlike cefoxitin.
- Differential in vitro effects suggest distinct mechanisms of action for cefoxitin and cefotaxime on macrophage cytokine release.
- These findings highlight the potential for antibiotic-driven modulation of immune responses, impacting experimental infection models and potentially clinical outcomes.