Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin.
The fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) 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 micrograms/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-gamma production was inhibited and IFN-gamma 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 micrograms/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-gamma synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription.
Department of Medical Microbiology, Lund University, Malmö General Hospital, Sweden.
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K
Riesbeck
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Forsgren
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D002939:Ciprofloxacin; D007371:Interferon-gamma