CP-115,953 stimulates cytokine production by lymphocytes
(1995) In Antimicrobial Agents and Chemotherapy 39(2). p.476-483- Abstract
The cytotoxic quinolone CP-115,953 specifically exerts its inhibitory effect upon eukaryotic topoisomerase II. CP-115,953 stimulates DNA cleavage mediated by topoisomerase II with a potency approximately 600 times greater than that of ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use. Because ciprofloxacin has been reported to strongly enhance interleukin-2 production, we considered it important to study the effect of CP-115,953 on interleukin-2 and gamma interferon (IFN-γ) mRNA and protein expression in mitogen-stimulated human peripheral blood lymphocytes. For comparison, novobiocin and the antineoplastic drug etoposide were also included in the study. CP-115,953 (25 μM) enhanced interleukin-2 mRNA... (More)
The cytotoxic quinolone CP-115,953 specifically exerts its inhibitory effect upon eukaryotic topoisomerase II. CP-115,953 stimulates DNA cleavage mediated by topoisomerase II with a potency approximately 600 times greater than that of ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use. Because ciprofloxacin has been reported to strongly enhance interleukin-2 production, we considered it important to study the effect of CP-115,953 on interleukin-2 and gamma interferon (IFN-γ) mRNA and protein expression in mitogen-stimulated human peripheral blood lymphocytes. For comparison, novobiocin and the antineoplastic drug etoposide were also included in the study. CP-115,953 (25 μM) enhanced interleukin-2 mRNA levels up to 8-fold and IFN-γ mRNA concentrations up to 6.5-fold. In contrast, ciprofloxacin (282 μM) induced mRNAs for interleukin-2 and IFN-γ up to 20- fold and 7.8-fold, respectively. However, CP-115,953 showed more prolonged kinetics of IFN-γ mRNA production than ciprofloxacin. At high concentrations (≥141 μM), ciprofloxacin was a greater inducer of interleukin-2 production and exhibited a higher level of stimulatory action than CP-115,953 on IFN-γ synthesis. At low concentrations, however, CP-115,953 (≤25 μM) was more potent than ciprofloxacin in inducing interleukin-2 and IFN-γ synthesis. Etoposide or novobiocin did not influence cytokine mRNA expression. Thus, among the topoisomerase II inhibitors tested, fluoroquinolones are unique in stimulating cytokine synthesis in lymphocyte cultures.
(Less)
- author
- Riesbeck, K. LU and Forsgren, A. LU
- organization
- publishing date
- 1995-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Antimicrobial Agents and Chemotherapy
- volume
- 39
- issue
- 2
- pages
- 476 - 483
- publisher
- American Society for Microbiology
- external identifiers
-
- scopus:0028855032
- pmid:7726518
- ISSN
- 0066-4804
- DOI
- 10.1128/AAC.39.2.476
- language
- English
- LU publication?
- yes
- id
- ba01afa6-505b-45f3-a69a-bfdbf7f84b12
- date added to LUP
- 2019-03-29 11:50:19
- date last changed
- 2024-01-01 00:30:48
@article{ba01afa6-505b-45f3-a69a-bfdbf7f84b12, abstract = {{<p>The cytotoxic quinolone CP-115,953 specifically exerts its inhibitory effect upon eukaryotic topoisomerase II. CP-115,953 stimulates DNA cleavage mediated by topoisomerase II with a potency approximately 600 times greater than that of ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use. Because ciprofloxacin has been reported to strongly enhance interleukin-2 production, we considered it important to study the effect of CP-115,953 on interleukin-2 and gamma interferon (IFN-γ) mRNA and protein expression in mitogen-stimulated human peripheral blood lymphocytes. For comparison, novobiocin and the antineoplastic drug etoposide were also included in the study. CP-115,953 (25 μM) enhanced interleukin-2 mRNA levels up to 8-fold and IFN-γ mRNA concentrations up to 6.5-fold. In contrast, ciprofloxacin (282 μM) induced mRNAs for interleukin-2 and IFN-γ up to 20- fold and 7.8-fold, respectively. However, CP-115,953 showed more prolonged kinetics of IFN-γ mRNA production than ciprofloxacin. At high concentrations (≥141 μM), ciprofloxacin was a greater inducer of interleukin-2 production and exhibited a higher level of stimulatory action than CP-115,953 on IFN-γ synthesis. At low concentrations, however, CP-115,953 (≤25 μM) was more potent than ciprofloxacin in inducing interleukin-2 and IFN-γ synthesis. Etoposide or novobiocin did not influence cytokine mRNA expression. Thus, among the topoisomerase II inhibitors tested, fluoroquinolones are unique in stimulating cytokine synthesis in lymphocyte cultures.</p>}}, author = {{Riesbeck, K. and Forsgren, A.}}, issn = {{0066-4804}}, language = {{eng}}, month = {{01}}, number = {{2}}, pages = {{476--483}}, publisher = {{American Society for Microbiology}}, series = {{Antimicrobial Agents and Chemotherapy}}, title = {{CP-115,953 stimulates cytokine production by lymphocytes}}, url = {{http://dx.doi.org/10.1128/AAC.39.2.476}}, doi = {{10.1128/AAC.39.2.476}}, volume = {{39}}, year = {{1995}}, }