Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin-1beta in human tendon-derived cells. A potential mechanism of fluoroquinolone-induced tendinopathy

Arthritis Rheum. 2002 Nov;46(11):3034-40. doi: 10.1002/art.10617.


Objective: To determine whether the fluoroquinolone antibiotic ciprofloxacin, which can cause tendon pain and rupture in a proportion of treated patients, affects the expression of matrix metalloproteinases (MMPs) in human tendon-derived cells in culture.

Methods: Cell cultures were derived from 6 separate tendon explants, and were incubated in 6-well culture plates for 2 periods of 48 hours each, with ciprofloxacin (or DMSO in controls) and interleukin-1beta (IL-1beta), alone and in combination. Samples of supernatant medium from the second 48-hour incubation were assayed for MMPs 1, 2, and 3 by Western blotting. RNA was extracted from the cells and assayed for MMP messenger RNA (mRNA) by semiquantitative reverse transcription-polymerase chain reaction, with normalization for GAPDH mRNA.

Results: Unstimulated tendon cells expressed low or undetectable levels of MMP-1 and MMP-3, and substantial levels of MMP-2. IL-1beta induced a substantial output of both MMP-1 and MMP-3 into cell supernatants, reflecting increases (typically 100-fold) in MMP mRNA, but had only minor effects on MMP-2 expression. Ciprofloxacin had no detectable effect on MMP output in unstimulated cells. Preincubation with ciprofloxacin potentiated IL-1beta-stimulated MMP-3 output, reflecting a similar effect on MMP-3 mRNA expression. Ciprofloxacin also potentiated IL-1beta-stimulated MMP-1 mRNA expression, but did not potentiate the output of MMP-1, and had no significant effects on MMP-2 mRNA expression or output.

Conclusion: Ciprofloxacin can selectively enhance MMP expression in tendon-derived cells. Such effects might compromise tendon microstructure and integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / adverse effects
  • Cells, Cultured
  • Ciprofloxacin / adverse effects
  • Ciprofloxacin / pharmacology*
  • Humans
  • Interleukin-1 / physiology*
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Musculoskeletal Diseases / chemically induced
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tendons / cytology*


  • Anti-Infective Agents
  • Interleukin-1
  • RNA, Messenger
  • Ciprofloxacin
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1