Local and Systemic Activation of the Mononuclear Phagocyte System in Aseptic Loosening of Total Hip Arthroplasty

Abstract

Osteoarticular prosthesis loosening involves recruitment, activation, and differentiation of mononuclear phagocytes, with a complex and still unclear interplay of local and systemic inflammation. We hypothesized that aseptic hip prosthesis loosening is bound to a coordinated systemic and local activation of the mononuclear phagocyte system (MPS), which can be demonstrated by simultaneous assessment of both compartments. We, therefore, compared systemic and synovial inflammatory cytokines, circulating monocyte activation state, and synovial fluid (SF) ability to induce osteoclastic differentiation. Twenty-seven patients undergoing total hip replacement for aseptic loosening were compared to 30 patients receiving total hip prosthesis for primary osteoarthritis. SF from aseptic loosening patients induced a more effective osteoclast-like differentiation of monocytic THP-1 cells in vitro and a proinflammatory pattern of cytokine production in these osteoclast-like cultures. On the contrary, SF from osteoarthritis patients did not favor osteoclastogenesis and exerted an anti-inflammatory effect through IL-10 upregulation and TNF-alpha inhibition. Peripheral blood monocytes of aseptic loosening patients were primed for activation, with higher TNF-alpha responses than their counterparts in the osteoarthritis group. Finally, cytokine enrichment in SF versus serum was observed in both patient groups: a fivefold increase in synovial TNF-alpha in aseptic loosening patients and a 14-fold increase in synovial IL-10 in osteoarthritis patients. The TNF-alpha/IL-10 ratio was elevated in both systemic and synovial settings from aseptic loosening patients with respect to osteoarthritis patients. Taken together, our results demonstrate the integrated activation of the MPS and suggest the possible use of cytokines in the laboratory workup of prosthesis aseptic loosening.