Interaction of cytokines in osteolysis

Han, Jae Dong; Shin, Joo Ho; Hwang, Hyun Chull; Kim, Do Yung; Cho, Won Ho; Im, Gun Il

Abstract

PURPOSE
Osteolysis has become a major cause of aseptic loosening in total hip arthroplasty. Macrophages phagocytose wear debris from implants and release the pro-inflammatory mediators such as IL-1beta, IL-6, TNF-alpha and nitric oxide. We evaluated the effects of metal patricles on the release of bone-associated cytokines and nitric oxide from J774 mouse macrophage cell line.
MATERIALS AND METHODS
Titanium-Aluminum-Vanadium (Ti6Al4V) and Cobalt-Chrome-Aluminium (CoCr) particles were loaded and nitric oxide production was measured indirectly by the nitrite assay. The effect on cell proliferation, and apoptosis were also investigated with non-isotopic proliferation assay, and ELISA to DNA and histone. The levels of two proinflammatory cytokines, IL-6 and TNF-alpha, were measured with ELISA. The modulatory effect of anti-inflammatory cytokine on the nitrite, IL-6 and TNF-alpha production was additionally investigated.
RESULTS
Nitrite levels increased after administration of Ti6Al4V and CoCr particle. IL-10 and IL-4 inhibited the production of nitrite with TiAl4V particle, but not in significant amount with CoCr particles. Cellular proliferative activity decreased and apoptosis increased after administration of Ti6Al4V and CoCr particle. Levels of IL-6 and TNF-a increased with both particles. IL-10 and IL-4 inhibited the production of IL-6 and TNF-alpha in varying degrees.
CONCLUSION
Our data confirmed the increased production of pro-inflammatory cytokines and nitric oxide with metal particles and the inhibitory effect of IL-10 and IL-4 on the production of these substances, and suggest differences in the specific action between different metal particles.