Fluorinated 4-quinolones induce hyperproduction of interleukin 2

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 micrograms/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 micrograms/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 micrograms/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.