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Interleukin‐1β and tumor necrosis factor are essential in controlling an experimental orthopedic implant‐associated infection
Author(s) -
Wang Yu,
Ashbaugh Alyssa G.,
Dikeman Dustin A.,
Zhang Jeffrey,
Ackerman Nicole E.,
Kim Sophie E.,
Falgons Christian,
Ortines Roger V.,
Liu Haiyun,
Joyce Daniel P.,
Alphonse Martin Prince,
Dillen Carly A.,
Thompson John M.,
Archer Nathan K.,
Miller Lloyd S.
Publication year - 2020
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24608
Subject(s) - tumor necrosis factor alpha , staphylococcus aureus , immunology , medicine , osteomyelitis , septic arthritis , monocyte , cytokine , arthritis , interleukin , implant , biology , surgery , bacteria , genetics
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.