Interleukin-1β and tumor necrosis factor are essential in controlling an experimental orthopedic implant-associated infection

Yu Wang, Alyssa G. Ashbaugh, Dustin A. Dikeman, Jeffrey Zhang, Nicole E. Ackerman, Sophie E. Kim, Christian Falgons, Roger V. Ortines, Haiyun Liu, Daniel P. Joyce, Martin Prince Alphonse, Carly A. Dillen, John M. Thompson, Nathan K. Archer, Lloyd S. Miller

Research output: Contribution to journalArticle

Abstract

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-1α (IL-1α), IL-1β, 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-1α, IL-1β, or TNF. Mice deficient in IL-1β or TNF (to a lesser extent) but not IL-1α had increased bacterial burden at the site of the OIAI throughout the 28-day experiment. IL-1β 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-1α- and IL-1β-deficient mice had impaired neutrophil recruitment whereas IL-1β-, TNF-, and IL-1R/TNF-deficient mice all had impaired recruitment of both neutrophils and monocytes. Therefore, IL-1β and TNF contributed to host defense against S. aureus OIAI and neutrophil recruitment was primarily mediated by IL-1β and monocyte recruitment was mediated by both IL-1β and TNF.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - Jan 1 2020

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Keywords

  • IL-1
  • Staphylococcus aureus
  • TNF
  • monocyte
  • neutrophil
  • orthopedic surgery

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Wang, Y., Ashbaugh, A. G., Dikeman, D. A., Zhang, J., Ackerman, N. E., Kim, S. E., Falgons, C., Ortines, R. V., Liu, H., Joyce, D. P., Alphonse, M. P., Dillen, C. A., Thompson, J. M., Archer, N. K., & Miller, L. S. (Accepted/In press). Interleukin-1β and tumor necrosis factor are essential in controlling an experimental orthopedic implant-associated infection. Journal of Orthopaedic Research. https://doi.org/10.1002/jor.24608