| 1. |
- Riesbeck, Kristian, et al.
(författare)
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Evidence that the antibiotic ciprofloxacin counteracts cyclosporine‐dependent suppression of cytokine production
- 1994
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 57:2, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- The fluoroquinolone antibiotic ciprofloxacin (cipro) has been reported to upregulate interleukin 2 and interferon-γ production in lectin-stimulated lymphocytes. The aim of this study was to elucidate whether cipro and the immunosuppressive agent CsA have antagonistic action on cytokine synthesis. Accumulation of IL-2 and IFN-γ protein and mRNA were analyzed in polyclonally (PHA or Con A) or alloantigen-stimulated human peripheral blood lymphocytes. CsA added simultaneously with PHA partially blocked cytokine synthesis. The present study also shows that cipro supplemented with CsA and PHA resulted in significant higher concentrations of IL-2 (up to 60 times) and IFN-γ (4.3 times) as compared with PHA and CsA alone. Similar results were obtained with primary mixed lymphocyte reactions. In parallel, a greater amount of IL-2 and IFN-γ mRNA was observed in lymphocytes incubated with both cipro and CsA as compared with CsA alone. Our results reveal that CsA-dependent inhibition of both IL-2 and IFN-γ expression is counteracted by high concentrations of cipro. These findings may be of importance in clinical transplantation.
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| 2. |
- Riesbeck, Kristian, et al.
(författare)
-
Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin
- 1994
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Ingår i: Immunopharmacology. - : Elsevier BV. - 0162-3109. ; 27:2, s. 155-164
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Tidskriftsartikel (refereegranskat)abstract
- The fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-γ (IFN-γ) in stimulated human peripheral blood lymphocytes. In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated (T cell mitogens or alloantigens) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin (5-80 μg/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-γ production was inhibited and IFN-γ mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro (20 μg/ml). EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction. In addition, EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells (NFAT-1) as compared to control cells without antibiotics. Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A. Taken together, cipro inhibited IFN-γ synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription.
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| 3. |
- Riesbeck, Kristian, et al.
(författare)
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Limited effects of temafloxacin compared with ciprofloxacin on T- lymphocyte function
- 1994
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804. ; 38:4, s. 879-882
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Tidskriftsartikel (refereegranskat)abstract
- Temafloxacin increased interleukin-2 production and mRNA levels and enhanced thymidine incorporation in stimulated lymphocyte cultures. Gamma interferon mRNA levels were unaffected. Temafloxacin also stimulated interleukin-2 gene induction, as revealed in a chloramphenicol acetyltransferase reporter gene system. However, temafloxacin exerted significantly weaker effects in these respects than did ciprofloxacin.
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| 4. |
- Riesbeck, Kristian, et al.
(författare)
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Superinduction of cytokine gene transcription by ciprofloxacin
- 1994
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Ingår i: Journal of Immunology. - 0022-1767. ; 153:1, s. 343-352
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Tidskriftsartikel (refereegranskat)abstract
- In addition to their antibacterial properties, certain antibiotics are also biologic response modifiers. The fluorinated 4-quinolone, ciprofloxacin, for example, up-regulates IL-2 and IFN-γ production in PBLs stimulated in vitro. In the present study, ciprofloxacin was shown to increase the levels of mRNA for IL-1α, IL-2 and its receptor, IFN-γ, IL-3, IL-4, granulocyte- macrophage/CSF, TNF-α, and lymphotoxin. As investigated with different T cell mitogens and alloantigens, the up-regulation of IL-2 production by ciprofloxacin was found to be independent of the mode of stimulation. Analysis of transcription activity showed that ciprofloxacin enhances IL-2 gene induction. The concentrations of nuclear factor of activated T cells (NF-AT-1) and AP-1 were also found to be increased by ciprofloxacin. Thus, ciprofloxacin interferes with a regulative pathway common to several cytokines.
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