title: Metallic but not ceramic wear particles increase prostaglandin E2 release and interleukin-1beta gene expression in human blood monocytes in vitro.
abstract: In this study the potential of clinically relevant alumina ceramic and metal wear particles to induce an in vitro inflammatory response was assessed in human monocytes and lymphocytes isolated from healthy donors by measuring prostaglandin E2 (PGE2) levels and mRNA expression of various pro-inflammatory cytokines. Bacterial lipopolysaccharide (LPS) was used as positive control. LPS significantly increased PGE2 levels in the incubation medium of monocyte cultures after 24 h. Alumina had no effect on PGE2 production, whereas metals induced a concentration-dependent increase in PGE2 release, that was statistically significant at the dose of 0.1 mg/ml. In lymphocytes, LPS elicited a weak but significant increase in PGE2 release, whereas both alumina and metals did not modify PGE2 amounts at any of the concentrations tested. The gene expression of a number of pro- and anti-inflammatory cytokines was assessed in monocytes and lymphocytes exposed to LPS, 0.1 mg/ml alumina or 0.1 mg/ml metals for 24 h. In monocytes, LPS caused a 2-fold increase in interleukin-1beta (IL-1beta) mRNA levels. The exposure of monocytes to metals resulted in a selective increase in IL-1beta mRNA accumulation (+48% compared to control). By contrast, alumina did not modify IL-1beta mRNA levels. None of the test substances elicited any response on purified lymphocyte population. These findings suggest that PGE2 production and IL-1 mRNA expression are a reliable marker to study the pro-inflammatory effects of wear debris in vitro. The lower activity of alumina compared to metals suggests that the former should be preferred in implants for its favorable biological and mechanical behavior.
authors.affiliation: Institute of Orthopedics, Catholic University School of Medicine, 00168 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galli
authors.forename: Caterina
authors.initials: C
authors.lastname: Toriani Terenzi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Falcone
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Pozzetto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tringali
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Santis
authors.forename: Mauro
authors.initials: M
authors.lastname: Vairano
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
authors.forename: Giacomo
authors.initials: G
authors.lastname: Pozzoli
mesh_terms: D000537:Aluminum Oxide / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002516:Ceramics / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008670:Metals / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D008670:Metals; D012333:RNA, Messenger; D015232:Dinoprostone; D000537:Aluminum Oxide