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CP-115,953 stimulates cytokine production by lymphocytes

Riesbeck, K. LU orcid and Forsgren, A. LU (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.

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author
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organization
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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}},
}