Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli

Abstract

Susceptibility to osteolysis after total hip arthroplasty (THA) varies between individuals. We examined whether patients susceptible to osteolysis (group I, n ¼ 34 subjects) after cemented Charnley THA have quantitatively different innate immune responses to pro-inflammatory stimuli versus patients without this susceptibility (group II, n ¼ 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), endotoxinstripped titanium particles (Ti) or endotoxin-stripped particles with adherent LPS added-back (TI þ LPS). Subjects returned 1 week later and the experimental protocol was repeated. Assays for mRNA induction for interleukin (IL)-1a, IL-1b, 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 þ LPS, and for IL-1a in response to Ti (P < 0.05). LPS or Ti þ 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. ß

Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNFα

“…This might suggests that fluid pressure recruited cells mainly from the bone marrow meanwhile titanium particles seemed to recruit cells from the soft tissue beneath the piston. We corroborated that titanium particle-induced osteolysis displays an up-regulation of a pro-inflammatory response and subsequent osteoclast activation as previously described in both animal models [Taki et al, 2005] and in vitro studies [Gordon et al, 2010]. TNFa, IL-1, and IL-6 were all up regulated at the mRNA level after 24 h, which might be related to osteoblastic and/or macrophage-driven stimulation of osteoclastogenesis.…”

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…However, those studies also showed that other factors modulate the biologic response to wear particles. Also consistent with the importance of other factors is the finding that monocyte production of proinflammatory cytokines in response to polyethylene and titanium wear particles varies greatly between individual donors [31,46]. The similar finding with different types of particles is not surprising because the different types of particles are thought to induce osteolysis through similar proinflammatory mechanisms [7,75,102,108].…”

The Change of Neutrophil Lymphocyte Ratio in Acute Appendicitis

“…But patients shows different responses to inflammatory stimuli [12,13]. This may introduce bias into certain study designs.…”

“…Gordon et al were determined, patients had different responses to inflammatory stimuli [13]. There are some individual differences against to inflammation between patients, therefore NLR will vary from person to person in response to inflammatory stimuli.…”