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Upregulatory effects of cefpimizole natrium on human leukocytes
1Department of Oral Surgery, Kochi Medical School, Japan.
Abstract:
Cefpimizole natrium (CPIZ), an antibiotic belonging to the cephalosporins, was examined regarding its influence on neutrophil functions. Neutrophil superoxide (O2-) generation increased by intravenous CPIZ in patients with maxillofacial diseases. In vitro examination revealed that CPIZ directly stimulates neutrophils to generate O2- in a dose-dependent manner, though the induction ability is not as strong as phorbol myristate acetate (PMA). Protein kinase C (PKC) activity in the neutrophil plasma membrane increased after CPIZ treatment, while the activity in the cytosol fraction decreased. CPIZ cooperated with biological response modifiers (BRMs) such as sizofilan, lentinan, OK-432, rIL-2 and rIFN-gamma in neutrophil O2- generation. Non-specific cytotoxicity against K562 cells and candida cells was also enhanced by neutrophil pretreatment with both CPIZ and one of the BRMs except for sizofilan and rIL-2. From these results it can be concluded that CPIZ directly enhanced neutrophil O2- generation and that these CPIZ activations are further beneficial to protection against bacterial infections.
Insights
Cefpimizole sodium (CPIZ), a cephalosporin antibiotic, enhances neutrophil superoxide generation, boosting immune response against bacterial infections. This antibiotic also synergizes with biological response modifiers to improve immune cell function.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Neutrophils play a critical role in the innate immune system, particularly in combating bacterial infections.
- Cephalosporin antibiotics, like Cefpimizole sodium (CPIZ), are widely used to treat bacterial infections.
- Understanding the immunomodulatory effects of antibiotics can reveal novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of Cefpimizole sodium (CPIZ) on neutrophil functions, specifically superoxide generation.
- To explore the potential synergistic effects of CPIZ with biological response modifiers (BRMs) on immune cell activity.
- To determine the impact of CPIZ on neutrophil-mediated cytotoxicity against target cells and pathogens.
Main Methods:
- In vivo administration of CPIZ to patients with maxillofacial diseases and in vitro stimulation of neutrophils.
- Measurement of neutrophil superoxide (O2-) generation and protein kinase C (PKC) activity.
- Co-incubation of neutrophils with CPIZ and various BRMs (sizofilan, lentinan, OK-432, rIL-2, rIFN-gamma).
- Assessment of non-specific cytotoxicity against K562 cells and Candida cells.
Main Results:
- Intravenous CPIZ administration increased neutrophil superoxide generation in patients.
- In vitro, CPIZ directly stimulated neutrophils to produce superoxide in a dose-dependent manner, affecting PKC activity.
- CPIZ demonstrated synergistic effects with several BRMs, enhancing neutrophil superoxide generation.
- Combined CPIZ and BRM treatment (excluding sizofilan and rIL-2) enhanced neutrophil cytotoxicity against K562 and Candida cells.
Conclusions:
- Cefpimizole sodium (CPIZ) directly enhances neutrophil superoxide generation, a key mechanism in fighting infections.
- CPIZ's immunomodulatory effects, particularly its synergy with BRMs, suggest potential for enhanced therapeutic outcomes in bacterial infections.
- The findings support the role of CPIZ in boosting innate immune responses beyond its direct antimicrobial activity.