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

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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.