Influence of Body Weight and Composition on Immune Recovery

Overview

Immune dysfunction in individuals with obesity, secondary to chronic inflammation, may have an acute impact on War fighter health and readiness, and subsequent lethality. Indeed, \~51% of military personnel ages 17 or older are overweight, and \~15% have obesity (ranging from 6.4% in the Marine Corps to 18.0% in the Army). In conjunction with in vitro functional tests to assess systemic immune function, the suction blister model is a minimally invasive procedure that allows in vivo assessment of immune function (i.e., skin barrier restoration), and related mechanisms (i.e., pro- and anti-inflammatory cytokine responses at the wound site during the early phases of wound healing), consequent to obesity. We have demonstrated that the blister wound model reliably assesses skin barrier restoration and immune function at the wound site; and that relatively modest sleep disruption degrades immune response at the site of the disrupted skin barrier and delays the initial restoration of the skin barrier. However, our prior work excluded participants with obesity (≥30 kg/m2), since obesity is associated with an altered inflammatory response which may subsequently impact the body's functional response to a skin wound. Prior studies have indicated that immune function and wound healing is perturbed in individuals with obesity versus those without obesity. Existing research mainly relied on blood biomarkers and in vitro tests to assess systemic immune function; however, incorporating the blister wound model permits evaluation of the functional immune response to obesity in addition to local immune response at the wound site. Further, military personnel with obesity may be more physically active than civilians with obesity, which could mitigate the effects of obesity on immune dysfunction. Therefore, the primary aim of this parallel-group study is to utilize a suction blister model and in vitro functional assays to examine differences in immune function between participants without obesity (BMI 18.5-24.9 kg/m2) and with obesity (BMI ≥ 30 kg/m2) and related mechanisms (e.g., local cytokine response at the wound site and circulating markers of inflammation). Research will be conducted in a laboratory environment using males and females with obesity (BMI ≥ 30 kg/m2) compared to normal weight (BMI 18.5-24.9 kg/m2) controls. Participants in the study described herein (n = 50; n = 25 with obesity and n = 25 lean) will undergo baseline testing and a period of dietary surveillance prior to induction of up to eight blisters via suction on participant's forearm, after which time the top layer of blisters will be removed to reveal the dermal layer of skin. The primary outcome measure is initial restoration of the skin barrier (via transepidermal water loss) and additional outcome measures include immune function (e.g., circulating markers of inflammation, cytokines at the blister site, and secretory immunoglobin) and nutrient status. Additionally, to assess the impact of BMI on skeletal muscle inflammation, a subset of volunteers (n = 12 with obesity and n =12 lean) will undergo a single muscle biopsy at the conclusion of skin barrier restoration. Findings from this study will determine if obesity affects the early phases of wound healing and whether further study is warranted, e.g., do stressors exacerbate immune decrements observed in obese individuals, or can nutrition counter-measures mitigate immune decrements given that micronutrient deficiency is common in individuals with obesity.