Misoprostol Inhibits Polymethylmethacrylate-Stimulated Lysosomal Degranulation and IL-1 Release from Neutrophils

Endoprosthetic orthopedic implants may loosen over time. The mechanism of this loosening process remains poorly understood. Wear debris sloughed from bone cement (polymethylmethacrylate, PMMA) and orthopedic implant materials (metal, ultrahigh-molecular-weight polyethylene) may stimulate inflammatory responses in phagocytic cells which populate the bone-implant interface (synovial-like membrane). This investigation aimed to determine whether the prostaglandin-E(1) (PGE(1)) analog misoprostol might modulate PMMA-stimulated phagocytic cell degranulation and the release of interleukins such as IL-1. Lysozyme and IL-1 release from PMMA-stimulated neutrophils in vitro were measured as approximately 0.07 &mgr;g per 10(6) cells per min and 4 pg per 10(6) cells per min, respectively. These rates decreased to 0.03 &mgr;g per 10(6) cells per min and 1.7 pg per 10(6) cells per min, respectively, after the addition of 50 nM misoprostol to the incubation medium. Misoprostol inhibited degranulation and cytokine release in a dose-dependent manner. Consequently, misoprostol modulates PMMA-stimulated inflammatory responses. These responses appear to be mediated by prostanoids, and the regulation of prostanoids at the bone-implant interface may modulate the release of inflammatory osteolytic mediators (PGE(2)) which contribute to implant loosening.