Fluorinated 4-quinolones induce hyperproduction of interleukin 2
(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
-
- pmid:2539601
- scopus:0004027896
- 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
- 2024-06-26 11:38:50
@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}}, }