Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro-inflammatory stimuli.
Susceptibility to osteolysis after total hip arthroplasty (THA) varies between individuals. We examined whether patients susceptible to osteolysis (group I, n = 34 subjects) after cemented Charnley THA have quantitatively different innate immune responses to pro-inflammatory stimuli versus patients without this susceptibility (group II, n = 28 subjects) at a mean of 14 years after primary surgery. Extracted peripheral blood mononuclear cells were stimulated for 3 h using endotoxin (lipopolysaccharide-LPS, 100 ng/mL), endotoxin-stripped titanium particles (Ti) or endotoxin-stripped particles with adherent LPS added-back (TI + LPS). Subjects returned 1 week later and the experimental protocol was repeated. Assays for mRNA induction for interleukin (IL)-1alpha, IL-1beta, IL-1Ra, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF) were made using quantitative real-time PCR. Although baseline levels of mRNA expression were slightly lower in group I, inducibility of mRNA expression was markedly greater in group I versus group II for all cytokines in response to LPS or Ti + LPS, and for IL-1alpha in response to Ti (P < 0.05). LPS or Ti + LPS stimulation also resulted in an increase in the IL-1/IL-1Ra mRNA ratio in group I versus group II (P < 0.05). mRNA induction was highly reproducible between subject visits (r > 0.7, P < 0.001). Osteolysis-susceptible patients show repeatable, quantitatively different patterns of innate cytokine gene expression in response to pro-inflammatory stimuli versus THA patients who do not display this susceptibility. These innate immune differences may contribute to the variation in osteolysis-susceptibility observed clinically between individuals.
Academic Unit of Bone Metabolism, Sorby Wing, Department of Human Metabolism, Northern General Hospital, University of Sheffield, Herries Road, Sheffield S5 7AU, United Kingdom.
Andrew
A
Gordon
Edward M
EM
Greenfield
Richard
R
Eastell
Endre
E
Kiss-Toth
Jeremy Mark
JM
Wilkinson
D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010014:Osteolysis / Q000235:genetics* / Q000276:immunology*; D020959:Polyethylene / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology / Q000601:surgery; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000378:metabolism; D012086:Reoperation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000276:immunology / Q000494:pharmacology
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D020959:Polyethylene; D014025:Titanium