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-1r1-KO mice exposed to titanium particles. Additionally, the formation of a periprosthetic fibro-inflammatory membrane in IL-1r1-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-1r1-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-1r1-KO mice in response to titanium particles. This may be responsible, in part, for the diminished periprosthetic membrane observed in IL-1r1-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.
Epstein
Noah J
NJ
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5341, USA.
Warme
Bryan A
BA
Spanogle
Joshua
J
Ma
Ting
T
Bragg
Bill
B
Smith
R Lane
RL
Goodman
Stuart B
SB
D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D007249:Inflammation / Q000209:etiology*; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011475:Prosthesis Failure; D017472:Receptors, Interleukin-1 / Q000502:physiology; D014025:Titanium / Q000009:adverse effects*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014025:Titanium