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Influence of chemotherapeutic agents on superoxide anion production by human polymorphonuclear leukocytes
N Hara1, Y Ichinose, A Motohiro
1Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka, Japan.
Abstract:
The effects of 11 chemotherapeutic agents on superoxide anion (O2-) production were examined in human polymorphonuclear leukocytes (PMNL). All drugs, except predonine, were found to suppress O2- production in PMNL. Adriamycin (doxorubicin), mitomycin C, vindesine, cisplatin, etoposide, nimustine, and pepleomycin suppressed O2- production at relatively low drug concentrations, whereas methotrexate, 5-fluorouracil and vincristine suppressed O2- production at high drug concentrations. Time-dependent suppression of O2- production was evaluated in four drugs, namely Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cisplatin, vindesine, and methotrexate. Only Adriamycin showed suppressive effect on PMNL-derived O2- production in a time-dependent manner. Production of O2- by PMNL is a fundamental element for its bactericidal activity. The authors' results showed suppression of O2- production in PMNL in the presence of chemotherapeutic agents. This indicates a relationship between chemotherapy drugs and susceptibility to infection. The influence of chemotherapeutic agents on O2- production by PMNL should thus be taken into consideration when assessing defense mechanisms and susceptibility to infection of patients treated with these drugs.
Insights
Chemotherapy drugs significantly suppress superoxide anion (O2-) production in human polymorphonuclear leukocytes (PMNL), impacting bacterial defense mechanisms. This finding highlights increased infection susceptibility in patients undergoing chemotherapy.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Superoxide anion (O2-) production by polymorphonuclear leukocytes (PMNL) is crucial for bactericidal activity.
- Chemotherapeutic agents are widely used but can affect immune cell function.
- Understanding the impact of chemotherapy on PMNL function is vital for patient care.
Purpose of the Study:
- To investigate the effects of 11 chemotherapeutic agents on O2- production in human PMNL.
- To determine the concentration-dependent and time-dependent effects of these agents on PMNL function.
- To assess the implications of these effects on patient susceptibility to infection.
Main Methods:
- Human PMNL were isolated and exposed to 11 different chemotherapeutic agents.
- Superoxide anion (O2-) production was measured in response to drug exposure.
- Time-dependent effects were evaluated for selected drugs (Adriamycin, cisplatin, vindesine, methotrexate).
Main Results:
- Ten out of 11 chemotherapeutic agents suppressed O2- production in PMNL.
- Suppression occurred at low concentrations for Adriamycin, mitomycin C, vindesine, cisplatin, etoposide, nimustine, and pepleomycin.
- Methotrexate, 5-fluorouracil, and vincristine suppressed O2- production at high concentrations.
- Adriamycin demonstrated a time-dependent suppression of PMNL-derived O2- production.
Conclusions:
- Chemotherapeutic agents significantly impair the O2- producing capacity of PMNL.
- This impairment suggests a potential link between chemotherapy and increased susceptibility to infections.
- Clinicians should consider the impact of chemotherapy on PMNL function when managing patients.