PSS--ROLE OF IL-1 INHIBITOR/FIBROBLAST STIMULATOR

这个项目的目标是解开 硬皮病，以便可能进行更有效的治疗 和/或预防措施。在之前的研究中，我们有 描述了一种6-9000分子量的白介素1抑制剂 (IL-1)，由人外周血单核细胞在培养中产生， 它有一个有趣的特征，就是充当刺激器 成纤维细胞。患者外周血单核细胞的培养 硬皮病患者会产生更多的IL-1 抑制物/成纤维细胞刺激物与来自 普通人。我们的研究计划旨在调查 这种物质来确定是否有其他特征 将其与涉及的致病机制联系在一起 硬皮病。这些研究将包括调查 单核细胞激活，与这种抑制物的产生有关， 单核细胞分泌增加的特性 IL-1抑制剂/激活剂的量。各种物质 已知可激活单核细胞，以及病毒感染 单核细胞，将进行检查，以确定是否有 选择性地使单核细胞产生这种抑制物，并且 是否有证据表明这种物质与硬皮病有关。更多 远端区域与该物质可能在 硬皮病也将被研究。IL-1的产生，以及 低湿重。IL-1抑制物/成纤维细胞刺激物将在 其他炎症和纤维化状态以确定后者是否 与抑制剂产量的选择性增加有关。 我们还将研究这种IL-1抑制剂对 成纤维细胞在相当大的dail中，包括它对 成纤维细胞增殖和分泌胶原及 糖胺聚糖。我们还计划研究它对其他 相关的IL-1活性，如胶原酶的刺激 由成纤维细胞生产。我们将检查组织以确定 抑制剂的存在和/或可能的生产 硬皮病和其他相关疾病涉及的组织，使用 一种特定的单抗，或现在的寡核苷酸探针 正在开发中。可能与此抑制物有相同之处 硬皮病血清因子先前被描述为成纤维细胞 有丝分裂原也将被调查。我们的长期目标是 开发早期诊断、更有效的治疗方法， 治疗或预防硬皮病。

The objectives of this project are to unravel the mystery of scleroderma in order to make possible more effective therapy and/or preventive measures. In previous studies we have described a 6-9,000 molecular weight inhibitor of interleukin-1 (IL-1), produced by human peripheral blood monocytes in culture, which has the interesting characteristic of acting as a stimulator of fibroblasts. Cultured peripheral blood monocytes from patients with scleroderma produce increased amounts of this IL-1 inhibitor/fibroblast stimulator in comparison with those from normal individuals. Our research plan is designed to investigate this substance to determine if there are other characteristics which link it to the pathogenic mechanisms involved in scleroderma. The studies will include the investigation of monocyte activation, in relation to production of this inhibitor, and the characteristics of monocytes which produce increased amounts of the IL-1 inhibitor/activator. Various substances known to activate monocytes, as well as virus infection of monocytes, will be examined to determine whether any may selectively cause monocytes to produce this inhibitor, and whether evidence relates such a substance to scleroderma. More distal areas relating to a possible role for this substance in scleroderma will also be explored. Production of IL-1, and the low m.w. IL-1 inhibitor/fibroblast stimulator will be examined in other inflammatory and fibrotic states to determine if the latter are associated with selective increases in inhibitor production. We will also examine the action of this IL-1 inhibitor on fibroblasts in considerably greater dtail, including its effect on fibroblast proliferation and secretion of collagen and glycosaminoglycans. We also plan to study its effects on other related IL-1 activities such as stimulation of collagenase production by fibroblasts. We will examine tissues to determine the presence and/or possible production of the inhibitor in involved tissues in scleroderma and other related conditions, using a specific monoclonal antibody, or oliogonuclecotide probes now being developed. Possible identity with this inhibitor with scleroderma serum factors previously described as fibroblast mitogens will also be investigated. Our long term objective is to develop methods for early diagnosis, more effective treatment, cure, or prevention of scleroderma.