Impact of Methamphetamine Induced IL-6 Production on Wound Healing and Inflammation

摘要 据估计，全世界甲基苯丙胺（METH）使用流行率为1.35亿人，其中超过10 在美国（US）的百万用户。慢性甲基苯丙胺滥用和依赖使使用者暴露于各种 一系列不利的身体和认知健康后果。药物如METH的给药通过 注射几乎立即产生欣快的效果，这是由于多巴胺在大脑中的大量积累。 中枢神经系统值得注意的是，每天大量使用METH的人经常会出现蚁化， 类似于在皮肤上或皮肤下爬行的昆虫。蚁化的结果是，使用者从事不断的皮肤 “采摘”，往往会导致形成溃疡，延迟关闭，并经常疤痕。明显缺乏 使用者的卫生状况也可能与较高的皮肤感染率相关。与METH相关的伤口 使用者是喘息中心和健康护理机构的重要伤口护理问题。此外，成本 每年治疗METH相关的慢性伤口的费用为我们的医疗保健带来了沉重的经济负担 系统虽然有大量的信息，造成的行为和认知缺陷的甲基， 对于吸毒者，缺乏关于其对伤口愈合和炎症的影响的知识。我 初步数据显示METH处理的小鼠具有减少的伤口愈合。此外，METH增加IL-6 在皮肤组织中的产生和这种细胞因子水平的升高可能在炎症中具有直接的致病作用。 IL-6可能受到多巴胺的调节，多巴胺可以激活炎性细胞。因此，我假设METH 改变白细胞募集，并通过多巴胺能激活增强IL-6的产生 加剧炎症反应，导致伤口愈合延迟。这项R15学术研究 卓越成就奖（AREA）旨在阐明 METH改变炎症反应并干扰伤口愈合，导致慢性伤口易受 微生物感染。本研究的目的有两个：（1）探讨METH对创伤的影响 多形核白细胞的募集和修复;（2）评估METH对IL-6的作用 在体内伤口愈合和炎症的情况下产生。我相信这个项目是相当大的 在药物滥用、皮肤病学和免疫学领域具有重要意义。预计这一跨学科的 该计划可能会推动未来发展的实际治疗干预措施的管理， 吸毒者的慢性伤口此外，一个地区奖将是主要支持我的研究在 纽约理工学院的骨科医学，加强该机构的研究环境和暴露 我们的学生明显更多的生物医学研究，这将大大提高他们追求的潜力 科学和健康相关的职业

Abstract The prevalence of methamphetamine (METH) use is estimated at ∼35 million people worldwide, with over 10 million users in the United States (US). Chronic METH abuse and dependence expose the user to a diverse range of adverse physical and cognitive health consequences. The administration of drugs such as METH via injection delivers almost immediate effects of euphoria due to the substantial accumulation of dopamine in the central nervous system. Significantly, heavy daily users of METH frequently develop formication, a sensation akin to insects crawling on or under the skin. The result of formication is that users engage in constant skin “picking,” often causing the formation of ulcers that have delayed closure and frequently scar. A marked lack of hygiene among users may also be correlated to higher rates of skin infections. Wounds associated with METH users are an important wound care problem at respite centers and healthcare institutions. In addition, the cost of treatment for METH-associated chronic wounds per year is a heavy economic burden to our healthcare system. Although there is substantial information on the behavioral and cognitive defects caused by METH in drug users, there is a dearth of knowledge regarding its impact on wound healing and inflammation. My preliminary data shows that METH treated mice had decreased wound healing. Also, METH increases IL-6 production in skin tissue and elevated levels of this cytokine may have a direct pathogenic role in inflammation. IL-6 may be regulated by dopamine which can activate inflammatory cells. Hence, I hypothesize that METH alters leukocyte recruitment and also enhances IL-6 production via dopaminergic activation exacerbating the inflammatory response leading to delay wound healing. This R15 Academic Research Enhancement Award (AREA) is designed to make major contributions in elucidating the mechanisms by which METH alters inflammatory responses and interferes with wound healing, leading to chronic wounds susceptible to microbial infections. There are two aims proposed: (1) investigate the impact of METH on wound polymorphonuclear leukocytes recruitment and repair in vivo; and (2) assess the role of METH on IL-6 production in the setting of wound healing and inflammation in vivo. I believe this project is of considerable significance in the fields of drug abuse, dermatology, and immunity. It is anticipated that this interdisciplinary program may advance the future development of practical therapeutic interventions for the management of chronic wounds in drug users. Furthermore, an AREA award would be the primary support for my research at the NYIT College of Osteopathic Medicine, strengthening the institution’s research environment and exposing significantly more of our students to biomedical research, which will greatly enhance their potential for pursuing scientific and health‐related careers.