Ability of Ni-containing biomedical alloys to activate monocytes and endothelial cells in vitro.
Nickel-containing alloys commonly are used in medical and dental applications that place them into long-term contact with soft tissues. The release of Ni ions from these alloys is disturbing because of the toxic, immunologic, and carcinogenic effects that have been documented for some Ni compounds. In particular, Ni ions in solution recently have been shown to cause expression of inflammatory mediators, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecules (ICAMs) from keratinocytes, monocytes, and endothelial cells. However, the ability of the solid alloys themselves to induce these inflammatory effects has not been demonstrated. An in vitro system was used to determine if Ni-containing biomedical alloys could cause secretion of either IL-1beta or TNF-alpha from monocytes or expression of ICAMs on endothelial cells. Pure nickel, titanium, and three biomedical alloys-18-8 stainless steel, NiTi, and Rexillium III-were evaluated. First, it was determined whether or not the alloys or pure metals could cause cytotoxicity to THP-1 human monocytes or human microvascular endothelial cells (HMVECs) by measuring the succinic dehydrogenase (SDH) activity of the cells. Then, using identical conditions of exposure, the secretion of IL-1beta or TNF-alpha from monocytes or ICAM-1 expression on the HMVECs was determined. Only pure nickel suppressed (by 48% compared to Teflon controls) the SDH activity of the HMVECs or THP-1 monocytes. No alloy or metal caused the HMVECs to express ICAM-1, but the NiTi alloy caused a significant (ANOVA/Tukey) secretion of IL-1beta from the THP-1 monocytes. Secretion of TNF-alpha induced by NiTi was detectable but not statistically significant. The levels of IL-1beta secretion from monocytes were sufficient to induce ICAM-1 expression on HMVECs. The release of Ni from the NiTi was a logical suspect in causing the IL-1beta secretion by monocytes, but its role was not confirmed since other alloys, such as Rexillium III, released the same quantities of Ni yet did not activate the THP-1 monocytes. Within the limitations of in vitro conditions, our results indicate that NiTi alloys pose a risk of promoting an inflammatory response in soft tissues by activating monocytes. Further study is needed to substantiate this finding in vivo.
Department of Oral Rehabilitation, School of Dentistry, Medical College of Georgia, Augusta, Georgia 30912-1260, USA.
J C
JC
Wataha
P E
PE
Lockwood
M
M
Marek
M
M
Ghazi
D000497:Alloys / Q000633:toxicity*; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects*; D009532:Nickel / Q000032:analysis / Q000633:toxicity*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014025:Titanium / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000497:Alloys; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009532:Nickel; D014025:Titanium; D013385:Succinate Dehydrogenase