IL-1β and TNF are essential in controlling an experimental orthopaedic implant associated infection.

Orthopedic implant-associated infection (OIAI) is a major complication that leads to implant failure. In preclinical models of Staphylococcus aureus OIAI, osteomyelitis and septic arthritis, interleukin-1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor (TNF) are induced, but whether they have interactive or distinctive roles in host defense are unclear. Herein, a S. aureus OIAI model was performed in mice deficient in IL-1 alpha, IL-1 beta, or TNF. Mice deficient in IL-1 beta or TNF (to a lesser extent) but not IL-1 alpha had increased bacterial burden at the site of the OIAI throughout the 28-day experiment. IL-1 beta and TNF had a combined and critical role in host defense as mice deficient in both IL-1R and TNF (IL-1R/TNF-deficient mice) had a 40% mortality rate, which was associated with markedly increased bacterial burden at the site of the OIAI infection. Finally, IL-1 alpha- and IL-1 beta-deficient mice had impaired neutrophil recruitment whereas IL-1 beta-, TNF-, and IL-1R/TNF-deficient mice all had impaired recruitment of both neutrophils and monocytes. Therefore, IL-1 beta and TNF contributed to host defense against S. aureus OIAI and neutrophil recruitment was primarily mediated by IL-1 beta and monocyte recruitment was mediated by both IL-1 beta and TNF.