Enhancement of interleukin-2 production in human lymphocytes by two new quinolone derivatives

Abstract

The effect of two quinolone derivatives, ciprofloxacin and ofloxacin, on the production of interleukin-2 (IL-2) was studied in human peripheral blood lymphocytes (PBL) and in a T-cell leukemia cell line (Jurkat) following phytohemagglutinin (PHA) stimulation. Both antimicrobial agents markedly increased IL-2 production in PHA-stimulated PBL cultures. No such effect was observed without PHA stimulation. The effect of the two quinolones on IL-2 production was both time and concentration dependent, reaching a 3-5 fold increase at a drug concentration of 50-100 micrograms/ml, following 24 h incubation. IL-2 synthesized in response to ciprofloxacin or ofloxacin stimulation, exhibited identical chromatographic properties and molecular weight to IL-2 synthesized at standard IL-2 inducing conditions. Only ciprofloxacin enhanced IL-2 production in PHA or in PHA and phorbol myristic acetate (PMA)-stimulated Jurkat cells. The stimulatory effect observed in Jurkat cells at optimal dose concentration (10-50 micrograms/ml), was at most 50% above control levels. In contrast to the effect of ciprofloxacin as a costimulator of IL-2 production in PHA-stimulated PBL, the drug excerted a prominent inhibitory effect on the incorporation of radioactive thymidine and amino acids into these cells. Ciprofloxacin, but not ofloxacin, enhanced interferon (IFN) production in PHA-induced PBL, whereas immunoglobulin M [IgM] production in a SKW6 cell line was enhanced only by ofloxacin.