Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Quinolones and glucocorticoids are frequently used drugs that may cause tendinopathy as a rare adverse effect. We exposed human tenocyte cultures to the steroid dexamethasone alone or in combination with either ciprofloxacin or levofloxacin at concentrations of 3 mg/L and 10 mg/L. At concentrations corresponding to peak levels in plasma and tissues during therapy (ca. 3-10 mg/L), ciprofloxacin caused a significant decrease in collagen type I and the beta(1)-integrin receptor. In contrast, no corresponding effect was induced by 3 mg/L levofloxacin. With both quinolones at 3 mg/L and 10 mg/L, the amount of matrix metalloproteinase-1 (MMP-1) and MMP-13 was increased. In addition, 3 mg/L ciprofloxacin and 10 mg/L levo. oxacin activated caspase-3. Apoptotic changes were confirmed by electron microscopy. Incubation of human tenocytes with dexamethasone decreased the main matrix protein collagen type I, the transmembrane beta(1)-integrin receptor and the cytoskeleton protein vinculin, but only at the high concentrations tested (0.1 mu M or 10 mu M). Concentrations of 0.1 mu M and 10 mu M dexamethasone increased the amount of MMPs and activated caspase-3 as an indicator of apoptosis. Combined exposure to quinolones and dexamethasone led to more pronounced effects in tenocyte cultures at most of the analysed endpoints. The clinical observations of an increased risk of quinolone-induced tendinopathy by glucocorticoids are supported by these in vitro data. (C) 2009 Published by Elsevier B.V. and the International Society of Chemotherapy.