LPS-MONOCYTE INTERACTIONS IN PERIODONTAL DISEASE

人单核细胞释放高水平白介素1(IL-1) 和前列腺素E2(PGE2)在细菌刺激下 脂多糖(LPS)。这些可溶的介体具有某些 促炎、免疫抑制和骨吸收 其特点可能在其发病机制中起重要作用。 牙周炎。最近，我们研究了人类的能力 单核细胞在处理后释放这些产物 从疑似牙周组织中分离出的几种脂多糖制剂 病原体。脂多糖制剂促进前列腺素E_2和IL-1的释放 具有以下相对效力：大直立狼菌 大于或等于鼠伤寒沙门氏菌 伴生放线杆菌大于类杆菌 中间层大于牙龈假单胞菌。在初步的临床试验中 研究中，从患有牙病的患者中分离出单核细胞。 全身性重度成人牙周炎或年龄匹配的患者 很少或根本没有依恋损失。重症患者 牙周炎患者释放的前列腺素E_2是对照组的2-3倍 用从细胞中分离的脂多糖制剂处理细胞 鼠伤寒沙门氏菌、中间类杆菌、牙周炎杆菌 和伴放线放线杆菌。令人惊讶的是，IL-1 重度牙周炎患者和对照组的释放情况相似。 这些发现表明，内毒素介导的前列腺素E_2从 单核细胞可能与个体的易感性有关 牙周炎。最近，我们已经确定伽马 干扰素，一种激活的T淋巴细胞的产物，可以特异性地 促单核细胞释放PGE2和IL-1的作用 类杆菌脂多糖，沙门氏菌未检出。我们建议研究 单核细胞对高限定性制剂的分泌反应 脂蛋白，有或没有伽马干扰素，在以下两种情况下的患者 严重牙周炎或无明显附着丧失。分泌物 PGE2和IL-1的含量将在启动之前确定 牙周治疗，在最初治疗后，立即进行 手术治疗，所有治疗结束后4个月。 前列腺素E_2用GC-MS定量，IL-1用GC-MS定量 由RIA提供。此外，我们还将评估单核细胞的分泌反应 对于从有限数量的局限化患者分离的细胞 严重的牙周炎。我们希望确定内毒素介导的 单核细胞释放PGE2是一种固有的反应，而不是 受牙周治疗的影响。

Human monocytes release elevated levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). These soluble mediators possess certain proinflammatory, immunosuppressive and bone resorbing characteristics and may be important in the pathogenesis of periodontitis. Recently, we have examined the capacity of human monocytes to release these products following treatment with several LPS preparations isolated from suspected periodontal pathogens. LPS preparations promoted PGE2 and IL-1 release with the following relative potencies: Wolinella recta greater than or equal to Salmonella typhimurium greater than Actinobacillus actinomycetemcomintans greater than Bacteroides intermedius greater than B. gingivalis. In a preliminary clinical study, monocytes were isolated from dental patients with generalized severe adult periodontitis or age matched patients with little or no attachment loss. Patients with severe periodontitis released 2-3 fold more PGE2 than control patients when cells were treated with LPS preparations isolated from Salmonella typhimurium, Bacteroides intermedius, B. gingivalis and Actinobacillus actinomycetemcomintans. Surprisingly, IL-1 release was similar for severe periodontitis patients and controls. These findings suggest that LPS-mediated secretion of PGE2 from monocytes may be related to the susceptibility of an individual to periodontitis. Recently, we have determined that gamma interferon, a product of activated T lymphocytes, can specifically potentiate PGE2 and IL-1 release from monocytes treated with Bacteroides LPS but not Salmonella. We propose to examine monocyte secretory response to highly defined preparations of LPS, with or without gamma interferon, in patients with either severe periodontitis or no significant attachment loss. Secretion of PGE2 and IL-1 will be determined prior to the initiation of periodontal therapy, after initial therapy, immediately following surgical therapy and 4 months after the completion of all therapy. PGE2 will be quantitated by GC-MS and IL-1 will be quantitated by RIA. In addition, we will assess monocyte secretory responses for cells isolated from a limited number of patients with localized severe periodontitis. We hope to establish that LPS-mediated PGE2 release from monocytes is an inherent response which is not affected by periodontal therapy.