Interleukin‐1 modulates periprosthetic tissue formation in an intramedullary model of particle‐induced inflammation

Interleukin‐1 (IL‐1) is a proinflammatory cytokine that has been implicated in wear‐debris associated total joint replacement failure. We hypothesized that the absence of the IL‐1 type‐1 receptor would mitigate the inflammatory response to titanium particles and decrease periprosthetic inflammatory tissue in a murine intramedullary rod model. Methods: An intramedullary rod with and without commercially pure titanium particles was placed in the femora of 24 wild type mice (WT) and 24 mice lacking a functional type‐1 receptor to IL‐1. Femora were analyzed histologically and by ELISA of organ culture explant supernatants. Results: The presence of titanium particles in WT mice stimulated increased expression of interleukin‐6 (IL‐6) and macrophage chemoattractant protein‐1 (MCP‐1) relative to rod only controls. In contrast, IL‐6 and MCP‐1 expression were diminished in IL‐lrl‐KO mice exposed to titanium particles. Additionally, the formation of a periprosthetic fibro‐inflammatory membrane in IL‐lrl‐KO mice was blunted at 2 weeks when compared to that in wild‐type mice. Inflammatory changes and the quality of periprosthetic bone of IL‐lrl‐KO mice was similar to WT mice in response to titanium particles. Conclusions: These results implicate IL‐1 as an important modulator in the local inflammatory response to intramedullary titanium particles. MCP‐1 appears to be significantly modulated in IL‐lrl‐KO mice in response to titanium particles. This may be responsible, in part, for the diminished periprosthetic membrane observed in IL‐lrl‐KO mice at 2 weeks. Expansion of this murine model of intramedullary particle‐induced inflammation to other gene targets may contribute to a more mechanistic understanding of wear‐debris associated prosthesis failure.