Clinical Investigations in Infectious and Autoimmune Diseases

免疫功能低下的患者表现出多种特发性皮肤和粘膜病变，包括皮炎、胃肠道和生殖道溃疡以及复发性口腔炎。本研究计划的目的之一是评估与免疫失调相关的粘膜炎症在hiv感染的口腔病变患者中的发病机制。一项使用局部沙利度胺的随机对照临床试验被启动，该试验作为几条调查线的载体，旨在调查口腔溃疡的发病机制和治疗，口腔溃疡是一种病因不明的自发性、复发性粘膜溃疡，在HIV/AIDS患者中持续存在并使人虚弱。除了粘膜病变，皮肤病变也可能成为慢性和衰弱，新的努力集中在治疗干预慢性不愈合的伤口。老年人的延迟愈合反应，以中性粒细胞和过量弹性蛋白酶为主，可以在动物模型中模拟，包括卵巢切除的啮齿动物和分泌性白细胞蛋白酶抑制剂（SLPI）敲除小鼠。使用这些模型，可以通过局部应用雌激素或具有抗炎和抗弹性特性的SLPI逆转延迟愈合。基于雌激素在局部逆转人类非愈合伤口中的成功应用，其他抑制炎症部位持续白细胞募集和过多弹性蛋白酶释放的新方法将被评估其促进愈合过程的功效。

Immunocompromised patients demonstrate a wide variety of idiopathic cutaneous and mucosal lesions including dermatitis, gastrointestinal and genital tract ulcerations, and recurrent aphthous stomatitis. One objective of this research program is to evaluate the pathogenesis of mucosal inflammation associated with immune dysregulation in HIV-infected patients with aphthous lesions. A randomized, controlled clinical trial using topical thalidomide was initiated which serves as a vehicle for several lines of inquiry directed towards investigating the pathogenesis and treatment of oral aphthous ulcers, which are spontaneous, recurrent mucosal ulcerations of unknown etiology, and which are persistent and debilitating in persons with HIV/AIDS. In addition to mucosal lesions, cutaneous lesions may also become chronic and debilitating, and new efforts are focusing on therapeutic intervention in chronic nonhealing wounds. The delayed healing response in the aged, characterized by a predominance of neutrophils and excess elastase, can be mimicked in animal models including ovariectomized rodents and secretory leukocyte protease inhibitor(SLPI) knockout mice. Using these models, delayed healing can be reversed by the topical application of estrogen or by SLPI which has anti-inflammatory and anti-elastase properties. Based on the successful application of estrogen topically in reversing human nnnonhealing wounds, other novel approaches for inhibiting the persistent leukocyte recruitment and overabundant elastase released at the inflammatory site will be evaluated for their efficacy in facilitating the healing process.