Modulation of IL-1β, IL-6, TNF-α and PGE2 by pharmacological agents in explants of membranes from failed total hip replacement

Introduction and goal Proinflammatory cytokines and prostaglandin E2 (PGE2) play an important role in the pathophysiology of osteolysis and implant loosening. The aim of this study was to evaluate the role of pharmacological agents in the inhibition of Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and PGE2 in explants of interface membranes from failed total hip replacements (fTHR). Material and methods Membranes from fTHR were retrieved (N=20) and explants were incubated for 72h in the absence or presence of tenidap at three different concentrations (5, 20 or 50μg/ml) or diclofenac (125μg/l). IL-1β, IL-6, TNF-α, and PGE2 levels were measured in the culture medium using ELISA Capture or EIA kits. Statistical analysis was done using the Mann–Whitney U-test. Results A statistically significant inhibition in IL-1β synthesis was found at tenidap concentrations of 20μg/ml (71.3%, P< 0.05) and 50μg/ml (79.3%,P< 0.02). Tenidap reduced IL-6 levels by 90.4% at 20μg/ml (P< 0.005) and 96.0% (P< 0.05) at 50μg/ml. Tenidap also reduced the synthesis of TNF-α by 66.9% (P< 0.05) and 77.4% at concentrations of 20μg/ml and 50μg/ml. Tenidap had a marked suppressive effect of over 90% (P< 0.0001) on PGE2 synthesis in all three concentrations. Diclofenac (125μg/l) decreased PGE2 production by 95% (P< 0.0001), but had no significant effect in IL-1β, IL-6, and TNF-α levels in the culture medium. Conclusion The ability to simultaneously suppress the release of proinflammatory cytokines and PGE2 may help control osteolysis and prevent aseptic loosening of THR. This effect could increase implant longevity and lead the way to the pharmacological treatment of this pathology. Copyright 2002 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International.