LPS-MONOCYTE INTERACTIONS IN PERIODONTAL DISEASE

人单核细胞释放升高水平的白细胞介素-1（IL-1） 和前列腺素E2（PGE 2），当用细菌刺激时， 脂多糖（LPS）。 这些可溶性介质具有一定的 促炎、免疫抑制和骨吸收 特征，并可能是重要的发病机制， 牙周炎 最近，我们研究了人类 单核细胞释放这些产品后处理 几种从疑似牙周炎组织中分离的LPS制剂 病原体 LPS制剂促进PGE 2和IL-1的释放 具有以下相对效力： 大于或等于鼠伤寒沙门氏菌大于 大于类杆菌的放线共生放线杆菌 中间值大于B。牙龈炎 在初步临床试验中， 在一项研究中，单核细胞分离自患有 全身性重度成人牙周炎或年龄匹配的患者 很少或没有附着损失。 重症 牙周炎患者释放的PGE 2是对照组的2-3倍 当细胞用分离自 鼠伤寒沙门氏菌、中间拟杆菌、B.牙龈 和放线共生放线杆菌（Actinobacillus actinomycetemcomintans）。 令人惊讶的是，IL-1 重度牙周炎患者和对照组的释放相似。 这些结果表明，LPS介导的PGE 2分泌， 单核细胞可能与个体对以下疾病的易感性有关： 牙周炎 最近，我们确定伽马射线 干扰素是活化T淋巴细胞的产物， 增强PGE 2和IL-1从用 类杆菌LPS而不是沙门氏菌。 我们建议研究 单核细胞分泌反应高度明确的制剂， LPS，有或没有γ干扰素，在患者中， 重度牙周炎或无明显附着丧失。 分泌 将在开始治疗前测定PGE 2和IL-1的含量 牙周治疗，初始治疗后，立即 手术治疗结束后4个月。 将通过GC-MS对PGE 2进行定量，并对IL-1进行定量 用放射免疫法 此外，我们将评估单核细胞分泌反应， 对于从有限数量的局部性 严重牙周炎。 我们希望建立LPS介导的 单核细胞释放PGE 2是一种固有的反应， 受到牙周治疗的影响。

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.