Emingil G, Coker I, Atilla G, Hüseyinov A
Ege University, School of Dentistry, Department of Periodontology, Izmir, Turkey.
J Periodontol. 2000 Jan;71(1):50-7. doi: 10.1902/jop.2000.71.1.50.
Cyclosporine A (CsA) is a potent immunosuppressant effectively used to prevent organ transplant rejection and also to treat several systemic diseases. CsA-induced gingival overgrowth (CsA GO) is the most widely seen side effect of this drug; its pathogenesis is not completely understood. The aim of the present study was to identify the role of leukotriene B4 (LTB4) and platelet activating factor (PAF) in the pathogenesis of CsA GO.
LTB4 and PAF levels were detected in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO, from patients with gingivitis and from periodontally healthy subjects. Plaque index, papilla bleeding index, and hyperplastic index were recorded at each study site. GCF samples and clinical data were obtained from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and purified by high-performance liquid chromatographic (HPLC) method and analyzed by radioimmunoassay (RIA). PAF was extracted from GCF samples passing through amberlit resin columns, purified by HPLC, and analyzed by RIA.
Total amounts of LTB4 and PAF in GCF were higher in CsA GO+ sites compared to the healthy sites from healthy controls. However, the amount of LTB4 and PAF elevation in CsA GO+ sites was not significantly higher than those in diseased sites. Clinical degrees of gingival inflammation were also similar between CsA GO+ and diseased sites. LTB4 and PAF total amounts in GCF were higher in CsA GO+ sites compared to CsA GO- sites in the same subjects, but this difference just failed to reach significance. Similar findings were obtained with concentration data.
The results of this study indicate that CsA therapy does not have a significant effect on GCF LTB4 and PAF levels and that gingival inflammation seems to be the main reason for their elevation. In CsA-treated patients, alterations in LTB4 and PAF levels might play a role in CsA GO through some asyet unknown mechanism. To our knowledge, this is the first report describing the levels of lipid mediators in GCF of CsA-treated patients. We assume that further studies will contribute to the understanding of the pathogenesis of CsA-induced gingival overgrowth.
环孢素A（CsA）是一种强效免疫抑制剂，有效用于预防器官移植排斥反应，也用于治疗多种全身性疾病。CsA诱导的牙龈增生（CsA GO）是该药物最常见的副作用；其发病机制尚未完全明确。本研究的目的是确定白三烯B4（LTB4）和血小板活化因子（PAF）在CsA GO发病机制中的作用。
检测接受CsA治疗且出现CsA GO的肾移植患者、牙龈炎患者和牙周健康受试者的龈沟液（GCF）样本中的LTB4和PAF水平。记录每个研究部位的菌斑指数、乳头出血指数和增生指数。GCF样本和临床数据取自：每位接受CsA治疗的患者中2个出现CsA GO的部位（CsA GO+）和2个未出现CsA GO的部位（CsA GO-）；每位牙龈炎患者的2个患病部位；以及每位临床牙周健康受试者的2个健康部位。使用C18柱通过固相法从样本中提取LTB4，通过高效液相色谱（HPLC）法纯化，并通过放射免疫测定（RIA）法进行分析。通过amberlit树脂柱从GCF样本中提取PAF，通过HPLC纯化，并通过RIA进行分析。
与健康对照的健康部位相比，CsA GO+部位GCF中LTB4和PAF的总量更高。然而，CsA GO+部位LTB4和PAF升高的量并不显著高于患病部位。CsA GO+部位和患病部位的牙龈炎症临床程度也相似。与同一受试者的CsA GO-部位相比，CsA GO+部位GCF中LTB4和PAF的总量更高，但这种差异刚刚未达到显著水平。浓度数据也得到了类似的结果。
本研究结果表明，CsA治疗对GCF中LTB4和PAF水平没有显著影响，牙龈炎症似乎是其升高的主要原因。在接受CsA治疗的患者中，LTB4和PAF水平的改变可能通过某种未知机制在CsA GO中起作用。据我们所知，这是第一份描述接受CsA治疗患者GCF中脂质介质水平的报告。我们认为进一步的研究将有助于理解CsA诱导的牙龈增生的发病机制。
