TNF response of macrophages to wear particles, and its modification by drugs

Tumour necrosis factor (TNF) is considered to be the initiator protein of p article disease leading to aseptic loosening of endoprostheses. The aim of the present study was to investigate the TNF response of the macrophage-lik e cells (MLC) to the periprosthetic particles typically found during revisi on surgery. For this purpose, particles of polyethylene (PE), pure titanium (Ti), chromium (Cr), cobalt (Co), alumina ceramic (Al2O3) and zirconium di oxide (ZrO2) were used. Additionally, the therapeutic effect of non-steroid al and steroidal drugs, biphosphonates and pentoxyfylline on PE particles w as investigated with the aim of differentiating drugs with, from those with out, a positive effect on aseptic loosening. Method: In an established macrophage model (Rader et al. 1999), THP1 cells (human monocytic cell line) were differentiated over a period of five days in the presence of vitamin D3 and GM-CSF in macrophage-like cells (MLC). To obtain a TNF profile of the different materials, 10(6) MLC were incubated with each of a range of different particle concentrations. For drug testing purposes 80x10(8) PE particles, which evoked a maximum TNF response, were applied together with increasing drug concentrations in the same manner. Th e supernatant was then investigated for TNF secretion using ELISA. Results: It was found that the greatest TNF response was provoked by Cc and PE particles, and was 25 and 23 times as high, respectively, in comparison with control. The smallest TNF secretion was seen with Al2O3 (4x control) and ZrO2 (5x control). At the recommended dose, non-steroidal anti-inflamma tory drugs (NSAIDs) produced no decrease in TNF secretion. The biphosphonat es, etidronate and ibendronate significantly reduced the TNF response of th e PE-stimulated macrophages (by 1/7 and 1/5, respectively). Therapeutic dos es of pentoxyfylline also led to a decrease of 1/5 in maximum TNF release. Conclusion: Ceramic articulating surfaces are superior to metal/metal or PE /PE matings in terms of the biological effects of their wear particles. At therapeutic doses, NSAIDs have no beneficial effect on the process of asept ic loosening. Certain biphosphonates and pentoxyfylline have a positive eff ect on aseptic loosening.