OBJECTIVE: To determine the effect of the quinolone antibiotic ciprofloxacin, on interleukin-6, interleukin-8, and nitrite production by human endothelial cells. DESIGN: Controlled cell culture experiments examining the immunomodulatory effects of an antibiotic. SETTING: University research laboratory attached to a large teaching hospital. SUBJECTS: A human endothelial cell line. MEASUREMENTS AND MAIN RESULTS: Cells were incubated with tumor necrosis factor-alpha and interleukin-1beta in the presence of a range of ciprofloxacin concentrations. Interleukin-6, interleukin-8, and nitrite concentrations were measured in culture supernatants after 24 hrs using enzyme immunoassay. Ciprofloxacin decreased interleukin-6 accumulation (p = .001). Interleukin-8 was decreased at lower ciprofloxacin concentrations (p = .017) but was increased at 100 microg/mL (p = .0039). Ciprofloxacin had no effect on nitrite accumulation (p = .38). CONCLUSIONS: Ciprofloxacin differentially modulates interleukin-6 and interleukin-8 expression. The response to infection is coordinated by a cascade of cytokines and other mediators. The widespread use of ciprofloxacin in patients with severe infections is likely to result in alterations in local concentrations of cytokines. Selective control of cytokine concentrations by antibacterial agents will clearly have important therapeutic implications and may be a future research consideration in antibiotic drug design.
OBJECTIVE: To determine the effect of the quinolone antibiotic ciprofloxacin, on interleukin-6, interleukin-8, and nitrite production by human endothelial cells. DESIGN: Controlled cell culture experiments examining the immunomodulatory effects of an antibiotic. SETTING: University research laboratory attached to a large teaching hospital. SUBJECTS: A human endothelial cell line. MEASUREMENTS AND MAIN RESULTS: Cells were incubated with tumor necrosis factor-alpha and interleukin-1beta in the presence of a range of ciprofloxacin concentrations. Interleukin-6, interleukin-8, and nitrite concentrations were measured in culture supernatants after 24 hrs using enzyme immunoassay. Ciprofloxacin decreased interleukin-6 accumulation (p = .001). Interleukin-8 was decreased at lower ciprofloxacin concentrations (p = .017) but was increased at 100 microg/mL (p = .0039). Ciprofloxacin had no effect on nitrite accumulation (p = .38). CONCLUSIONS:Ciprofloxacin differentially modulates interleukin-6 and interleukin-8 expression. The response to infection is coordinated by a cascade of cytokines and other mediators. The widespread use of ciprofloxacin in patients with severe infections is likely to result in alterations in local concentrations of cytokines. Selective control of cytokine concentrations by antibacterial agents will clearly have important therapeutic implications and may be a future research consideration in antibiotic drug design.