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Ciprofloxacin enhances T cell function by modulating interleukin activities
K G Stünkel1, G Hewlett, H J Zeiler
1Bayer AG, Pharma Research Centre, Wuppertal, Germany.
Abstract:
Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity. CIP (0.1-30 micrograms/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens. In addition, CIP increased the amount of IL-2 found in the supernatants of phytohaemagglutinin (PHA)-stimulated human PBL. The presence of CIP in the medium (0.3-10 micrograms/ml) increased the levels of IL-1 found in the culture supernatants of adherence-enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide. In contrast there was no effect of CIP on the release of IL-1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431. CIP alone had no influence on the basal release of IL-2 by NOB-1 cells, a T cell line that responds to IL-1 with an increase in IL-2 synthesis, but, in combination with recombinant IL-1, CIP significantly enhanced the release of IL-2 by these cells. The results of this study suggest that CIP modulates the immune response at two levels--the production of IL-2 by activated T cells and the production of IL-1 by activated monocyte/macrophages. However, CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively. Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.
Insights
Ciprofloxacin (CIP) enhances immune responses by boosting DNA synthesis in mouse spleen cells and human lymphocytes. It also increases Interleukin-2 (IL-2) and Interleukin-1 (IL-1) production, suggesting modulation of T cell and macrophage functions.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Ciprofloxacin (CIP) is a quinolone antibiotic with broad-spectrum antibacterial activity.
- The immunomodulatory effects of ciprofloxacin are not fully understood.
Purpose of the Study:
- To investigate the effect of ciprofloxacin on immune cell DNA synthesis and cytokine production.
- To determine if ciprofloxacin modulates T cell and/or monocyte/macrophage functions.
Main Methods:
- Assessed DNA synthesis in mouse spleen cells and human peripheral blood lymphocytes (PBL) stimulated with mitogens or alloantigens in the presence of CIP.
- Measured Interleukin-2 (IL-2) and Interleukin-1 (IL-1) levels in cell culture supernatants.
- Evaluated the effect of CIP on primary antibody responses in vitro and in vivo.
Main Results:
- Ciprofloxacin (0.1-30 µg/ml) enhanced DNA synthesis in activated mouse spleen cells and human PBL.
- CIP increased IL-2 production in phytohemagglutinin (PHA)-stimulated human PBL.
- CIP augmented IL-1 release from activated mouse macrophages and human monocyte/macrophages, but not from freshly isolated monocytes or keratinocytes.
- CIP enhanced IL-2 release from a T cell line in combination with IL-1.
- CIP did not affect primary antibody responses in vitro or in vivo.
Conclusions:
- Ciprofloxacin modulates the immune response by enhancing T cell function and macrophage/T cell interactions.
- The immunomodulatory effects of CIP appear to be specific to T cell and monocyte/macrophage pathways, not affecting primary antibody production.