Ciprofloxacin reduces the stimulation of prostaglandin E2 output by interleukin-1β in human tendon-derived cells

Objective. Fluoroquinolone antibiotics such as ciprofloxacin can induce tendon pathology and have various effects on tendon-derived cells in culture. We are investigating whether ciprofloxacin modifies signalling responses in tendon cells. Methods. Human Achilles tendon-derived cells were preincubated with or without ciprofloxacin (50 mug/ml) and were then challenged with interleukin-1beta (IL-1beta, 1 ng/ml) for up to 48 h. Prostaglandin E-2 (PGE(2)) output was assayed by ELISA. The expression of cyclooxygenase-2 (COX-2) was examined by Western blotting. Results. IL-1beta stimulated a substantial and prolonged increase in the output of PGE(2). Preincubation with ciprofloxacin reduced IL-1beta-induced PGE(2) output at all times tested; the reduction at 48 h was 69% (99% confidence interval 59-79%; 15 experiments). Norfloxacin and ofloxacin also reduced PGE(2) output. However, ciprofloxacin did not affect the induction of COX-2 by IL-1beta, measured at 4 or 48 h. Conclusions. Ciprofloxacin reduces IL-1beta-induced PGE(2) output in tendon-derived cells. The reduction in PGE(2) output could modulate various cellular activities of IL-1beta, and may be implicated in fluoroquinolone-induced tendinopathy.