Wataha J C, Lockwood P E, Marek M, Ghazi M
Department of Oral Rehabilitation, School of Dentistry, Medical College of Georgia, Augusta, Georgia 30912-1260, USA.
J Biomed Mater Res. 1999 Jun 5;45(3):251-7. doi: 10.1002/(sici)1097-4636(19990605)45:3<251::aid-jbm13>3.0.co;2-5.
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.
含镍合金常用于医疗和牙科应用中，使其与软组织长期接触。由于已证明某些镍化合物具有毒性、免疫和致癌作用，这些合金中镍离子的释放令人担忧。特别是，最近已表明溶液中的镍离子会导致角质形成细胞、单核细胞和内皮细胞表达炎症介质，如白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和细胞间粘附分子（ICAM）。然而，固态合金本身诱导这些炎症效应的能力尚未得到证实。使用体外系统来确定含镍生物医学合金是否会导致单核细胞分泌IL-1β或TNF-α，或内皮细胞上ICAM的表达。对纯镍、钛以及三种生物医学合金——18-8不锈钢、镍钛合金和Rexillium III进行了评估。首先，通过测量细胞的琥珀酸脱氢酶（SDH）活性，确定合金或纯金属是否会对THP-1人单核细胞或人微血管内皮细胞（HMVEC）产生细胞毒性。然后，在相同的暴露条件下，确定单核细胞分泌IL-1β或TNF-α，或HMVEC上ICAM-1的表达。只有纯镍抑制（与聚四氟乙烯对照相比降低48%）了HMVEC或THP-1单核细胞的SDH活性。没有合金或金属导致HMVEC表达ICAM-1，但镍钛合金导致THP-1单核细胞显著（方差分析/图基检验）分泌IL-1β。镍钛合金诱导的TNF-α分泌可检测到，但无统计学意义。单核细胞分泌的IL-1β水平足以诱导HMVEC上ICAM-1的表达。镍从镍钛合金中的释放是导致单核细胞分泌IL-1β的合理怀疑对象，但其作用尚未得到证实，因为其他合金，如Rexillium III，释放的镍量相同，但未激活THP-1单核细胞。在体外条件的限制范围内，我们的结果表明，镍钛合金有通过激活单核细胞在软组织中引发炎症反应的风险。需要进一步研究以在体内证实这一发现。
