Fibroblast expression of C-C chemokines in response to orthopaedic biomaterial particle challenge in vitro

C-C chemokines are soluble mediators that occur in a periprosthetic granulo ma and influence recruitment, localization and activation of inflammatory c ells. This studs, tested effects of titanium and polymethylmethacrylate (PM MA) particles on expression of selected C-C chemokines in cultured human fi broblasts. The C-C chemokines analyzed included monocyte chemoattractant pr otein-1. 2 (MCP-1. 2). monocyte inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation, normal T-cell expressed and secreted protein (RANTES). Interleukin-1 beta (IL-1 beta) served Lis a known stimulator of c hemokine release while interleukin-6 (IL-6) expression served as a marker f or fibroblast activation. Protein and mRNA signal levels were determined by ELISA and RT-PCR. respectively. The results demonstrated that exposure of fibroblasts to titanium and PMMA particles resulted in increased release of MCP-1 in a dose- and time-dependent manner. After 24 h. titanium particles maximally upregulated MCP-1 release 7-fold while PMMA particles increased MCP-1 levels 2-fold. when compared to unchallenged fibroblasts. MCP-2, MIP- 1 alpha and RANTES levels remained unchanged Following exposure of fibrobla sts to titanium or PMMA particles at any concentration or time point tested . However. IL-1 beta stimulated release of MCP-1, MCP-2. and RANTES. but no t MIP-1 alpha from the fibroblasts. IL-1 beta, not particles, exhibited the most prominent effect on MCP-1 mRNA levels. Increased release of MCP-1 fro nt fibroblasts exposed to titanium and PMMA particles coincided with increa sed release of IL-6. This study suggests that release of chemoattractant fa ctors from fibroblasts localized in periprosthetic membranes enhances the c hronic inflammatory process leading to bone resorption and implant loosenin g. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd . All rights reserved.