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

Abstract

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-I 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 ELTSA.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-1 rl -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-I 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.

Interleukin-1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model

“…This is evidenced by the inducible serum IL-1β and IL-6 in injected WT mice when compared with IL-1R1 -/ -mice lacking functional receptors to IL-1β, or control mice without IL-1β injection (these mice did not have inducible production of serum IL-1β and IL-6). These findings were in agreement with previous studies that reported that IL-1β is a significant mediator in initiation of the immune response (26,27). The present study additionally assayed the serum levels of IL-6 to confirm that the increase in IL-1β was due to induction instead of exogenous injection.…”

Comparison of the roles of IL-1, IL-6, and TNFα in cell culture and murine models of aseptic loosening

“…Despite the abundant evidence described in the previous paragraphs suggesting an association between aseptic loosening and the pro-inflammatory cytokines, there is little experimental evidence directly demonstrating a role for IL-1 or IL-6 in either in vitro or in vivo models of aseptic loosening. For example in the murine femoral model, knock out of the IL-1 receptor blocked particle-induced inflammation but not particle-induced osteolysis [17]. Similarly, neutralizing antibodies to IL-1 did not block osteolysis in an organ culture model of aseptic loosening [25].…”

“…It is upregulated in aseptic loosening [4,6,7,15,16] and by wear particles in vitro [1][2][3] and in vivo [8,9]. Blockage of IL-1 activity inhibits particle-induced inflammation and osteoclast differentiation, respectively, in the murine femoral and air pouch models [17,18]. Moreover, a polymorphism in the gene that encodes the IL-1 receptor antagonist is also associated with an increased frequency of aseptic loosening [19].…”

Inhibiting wear particles-induced osteolysis with naringin

“…Moreover, the mouse model of osteolysis even confirmed the central role of inflammatory cytokines, such as TNF-α and IL-1, in wear particles-induced osteolysis [8,9]. As a further step, osteoclastogenesis and the activation of osteoclasts lead to peri-prosthetic osteolysis and implant aseptic loosening [10].…”