Fluorinated 4-quinolones induce hyperproduction of interleukin 2
Riesbeck, K. LU
; Andersson, J.
; Gullberg, M.
and Forsgren, A.
LU
(1989)
In Proceedings of the National Academy of Sciences of the United States of America
86(8).
p.2809-2813
- Abstract
The fluorinated 4-quinolones are a 'new' group of antibiotics with a broad antibacterial spectrum. They are already widely used in clinical practice. Previous studies have shown that these drugs increase the uptake of [3H]-thymidine into DNA of mitogen-stimulated lymphocytes but inhibit cell growth and immunoglobulin secretion. This study shows that the 4-quinolones strongly (up to 100 times) increase the recovery of interleukin 2 (IL-2) in culture supernatants of phytohemagglutinin (PHA)-stimulated normal human lymphocytes and also prolong the kinetics of IL-2 production. The effect was significant at clinically achievable concentrations (5 μg/ml). In addition to hyperproduction of IL-2, the level of RNA hybridizing with a... (More)
The fluorinated 4-quinolones are a 'new' group of antibiotics with a broad antibacterial spectrum. They are already widely used in clinical practice. Previous studies have shown that these drugs increase the uptake of [3H]-thymidine into DNA of mitogen-stimulated lymphocytes but inhibit cell growth and immunoglobulin secretion. This study shows that the 4-quinolones strongly (up to 100 times) increase the recovery of interleukin 2 (IL-2) in culture supernatants of phytohemagglutinin (PHA)-stimulated normal human lymphocytes and also prolong the kinetics of IL-2 production. The effect was significant at clinically achievable concentrations (5 μg/ml). In addition to hyperproduction of IL-2, the level of RNA hybridizing with a human IL-2 cDNA probe was also intensely elevated (16-32 times) in PHA-stimulated lymphocytes cultured with ciprofloxacin (80 μg/ml). The mechanism responsible for 4-quinolone-mediated effects on T cells is at present unclear, but evidence is presented that suggests the effect is not exerted at the level of protein kinase C activation. Ciprofloxacin at 80 μg/ml also decreased the expression of IL-2 receptors measured by immunofluorescence with CD 25 antibodies and a radiolabeled IL-2 binding assay. At the same concentration of ciprofloxacin, there was a very low expression of the transferrin receptor and the cell size increased very little in human lymphocytes after PHA stimulation. The enhanced IL-2 production by 4-quinolones may contribute to side effects reported when these drugs are used for treatment of patients.
(Less)
- author
- Riesbeck, K.
LU
; Andersson, J.
; Gullberg, M.
and Forsgren, A.
LU
- organization
- publishing date
- 1989-01-01
- type
- Contribution to journal
- publication status
- published
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 86
- issue
- 8
- pages
- 2809 - 2813
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:0004027896
- pmid:2539601
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.86.8.2809
- language
- English
- LU publication?
- yes
- id
- 6fc3a35b-b788-44c4-a4b8-12e46a2f1370
- date added to LUP
- 2019-03-22 10:57:57
- date last changed
- 2024-02-14 22:20:36
@article{6fc3a35b-b788-44c4-a4b8-12e46a2f1370,
abstract = {{<p>The fluorinated 4-quinolones are a 'new' group of antibiotics with a broad antibacterial spectrum. They are already widely used in clinical practice. Previous studies have shown that these drugs increase the uptake of [<sup>3</sup>H]-thymidine into DNA of mitogen-stimulated lymphocytes but inhibit cell growth and immunoglobulin secretion. This study shows that the 4-quinolones strongly (up to 100 times) increase the recovery of interleukin 2 (IL-2) in culture supernatants of phytohemagglutinin (PHA)-stimulated normal human lymphocytes and also prolong the kinetics of IL-2 production. The effect was significant at clinically achievable concentrations (5 μg/ml). In addition to hyperproduction of IL-2, the level of RNA hybridizing with a human IL-2 cDNA probe was also intensely elevated (16-32 times) in PHA-stimulated lymphocytes cultured with ciprofloxacin (80 μg/ml). The mechanism responsible for 4-quinolone-mediated effects on T cells is at present unclear, but evidence is presented that suggests the effect is not exerted at the level of protein kinase C activation. Ciprofloxacin at 80 μg/ml also decreased the expression of IL-2 receptors measured by immunofluorescence with CD 25 antibodies and a radiolabeled IL-2 binding assay. At the same concentration of ciprofloxacin, there was a very low expression of the transferrin receptor and the cell size increased very little in human lymphocytes after PHA stimulation. The enhanced IL-2 production by 4-quinolones may contribute to side effects reported when these drugs are used for treatment of patients.</p>}},
author = {{Riesbeck, K. and Andersson, J. and Gullberg, M. and Forsgren, A.}},
issn = {{0027-8424}},
language = {{eng}},
month = {{01}},
number = {{8}},
pages = {{2809--2813}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Fluorinated 4-quinolones induce hyperproduction of interleukin 2}},
url = {{http://dx.doi.org/10.1073/pnas.86.8.2809}},
doi = {{10.1073/pnas.86.8.2809}},
volume = {{86}},
year = {{1989}},
}