Abstract
Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 ± 0.3 vs. 1.3 ± 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1β and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 ± 0.6 vs. 4.2 ± 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.
Introduction
Altered energy balance can impair immune function and the response to vaccines in children [1]. In particular, the adverse impact of under-nutrition on immunity and infectious diseases in children is substantial and well-studied. But far less is known about the immune effects of other abnormal conditions of energy balance such as obesity, now a virtual epidemic in children in many areas of the world [2]. There are emerging data to suggest that in otherwise healthy children, obesity and levels of physical activity can, indeed, alter immune and inflammatory function [3–5]. For example, in adults, Weber and coworkers [6] and in children, Simo-Minana and coworkers [7] found reduced antibody responsiveness to hepatitis B vaccine in obese individuals.
The mechanisms for this impaired responsiveness to hepatitis B are not known, nor is it known whether antibody titers to other vaccines are also influenced by obesity. Mechanical factors, such as differences in concentration and volume of distribution of the vaccine in obese compared with normal weight individuals could play a role [8]. Alternatively, the impaired response to vaccines might be related to the chronic, low-level inflammatory state (characterized by elevated cytokines such as IL-6 and TNF-a) now known to be associated with obesity in adults and children [9].