Dose-dependent cytotoxicity and modulation of catabolic cytokine expression by teicoplanin in human articular chondrocytes

Intra-articular administration of teicoplanin is a cost-effective therapeutic strategy for septic arthritis. Although teicoplanin has been reported to induce cytotoxicity in multiple cell types, the effects on human articular chondrocytes remain insufficiently characterized. In this study, primary human articular chondrocytes were subjected in vitro to increasing concentrations of teicoplanin (10, 50, 100, 200, and 400 μg/mL) to assess dose-dependent toxicity. Since inflamed cells exhibit altered biological responses, additional experiments were performed using interleukin-1 beta (IL-1β)-stimulated chondrocytes. High concentrations of teicoplanin (≥ 200 μg/mL) induced marked chondrotoxicity, while exposure to 100 μg/mL significantly reduced cell viability and proliferation in normal chondrocytes. Cellular senescence was observed following combined IL-1β and teicoplanin treatment; however, glycosaminoglycan production was not affected. Teicoplanin did not further modulate IL-1β-induced suppression of anabolic gene expression, including aggrecan, type II collagen, and tissue inhibitor of metalloproteinase-1. Similarly, the IL-1β-driven upregulation of pro-inflammatory and catabolic mediators-IL1B, IL6, matrix metalloproteinase-3 (MMP3), and MMP9-was not significantly changed by teicoplanin at the mRNA level. Consistently, the secretion of IL-1β, IL-6, and MMP-3 remained unchanged in IL-1β-stimulated chondrocytes following teicoplanin exposure. In conclusion, teicoplanin exhibits dose-dependent chondrotoxicity: concentrations ≥100 μg/mL impair chondrocyte viability, whereas concentrations ≤50 μg/mL are biologically tolerable. These findings provide toxicological evidence that local teicoplanin concentrations should be carefully controlled during intra-articular administration, supporting the use of the lowest concentration capable of achieving bactericidal activity while minimizing chondrotoxicity in the treatment of septic arthritis.