Different Profiles of Toll-like Receptors (TLRs) Expressions in Aseptic Loose Periprosthetic Tissues and Septic Synovial Membranes around Total Hip Implants

INTRODUCTION: Total hip replacement (THR) is a procedure that reliably provides pain relief and improves daily activity for patients suffering from destructive end stage hip joint disease. The main long-term complication of THR surgery is prosthetic loosening often combined with osteolysis. The causes of loosening are mainly divided into two major categories. One is the septic loosening caused by implant infection and the other one is the so called aseptic loosening caused by foreign body inflammation against adhesive and abrasive wear debris and by delayed-type hypersensitivity reaction against self modified by metal ions formed as a result of corrosion. Toll-like receptors (TLRs) are mammalian homologue of Toll receptor, which was originally identified in Drosophila [1]. TLRs are transmembrane proteins of inflammatory cells and essential players in the recognition of microbial (pathogen-associated molecular patterns; PAMPs, dead or alive) and endogenous (alarmins) signals [2], which together form the so called “danger signals”. Endogenous alarmins and exogenous PAMPs can be considered subgroups of a larger set, the damage associated molecular patterns (DAMPs) [3]. They stimulate inflammatory responses via TLRs, but provide also the danger signal to adaptive immune responses, which may induce production of osteolytic inflammatory cytokines found in aseptic loose interfacial membrane. As inflammatory molecules play important roles in not only innate immune responses, but also foreign body reactions, the present work was performed to assess the eventual presence and response of some key TLRs in the “so called” aseptic loosening and septic artificial hip joints.