Immunotoxicity and Environment: Immunodysregulation and Systemic Inflammation in Children

Abstract

Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.

Exposure to Urban Air Pollution and Bone Health in Clinically Healthy Six-year-old Children

“…The marked reduction of peripheral blood neutrophils observed in highly exposed Mexico City children in this work and in previous studies, along with high concentrations of endothelin-1, have been taken as strong evidence for endothelial activation and inflammation (4,6) Moreover, the increase in monocytes has been described upon exposure to particulate matter (49). An interesting association in this work is the positive relationship between body fat and the numbers of peripheral neutrophils, as well as between monocytes and IL-6 concentrations in keeping with the literature pointing to low-grade systemic infl ammation related to higher levels of body fat in children (50,51).…”

“…TLR4 plays a critical role in the activation of IL-6 producing leukocytes (32) and LPS promotes osteoclast activity and bone resorption (37). Both associations are also very relevant in Mexico City where children are exposed to signifi cant concentrations of lipopolysaccharides associated with particulate matter (6). Since 85 % of the Mexican population lacks the Asp299Gly Toll-like receptor-4 (TLR-4) polymorphism associated with a blunted response to lipopolysacharide (Calderón-Garcidueñas personal data), most Mexican children will be responsive to LPS and the activation of TLR4.…”

“…There is evidence that exposure to air pollution can result in long-lasting health problems (3)(4)(5)(6)(7)(8)(9)(10). Vitamin D defi ciency and rickets are associated with air pollution, indoor confi nement during the day, residency at higher altitudes and darker skin pigmentation (11,12).…”

Exposure to Air Pollutants and Disease Activity in Juvenile‐Onset Systemic Lupus Erythematosus Patients

“…Over the last 20 years, exposure to fossil fuel combustion has attracted significant medical interest. Many studies have demonstrated that current levels of air pollutants contribute to cardiovascular and respiratory morbidity and mortality in adults and children (2,3,(12)(13)(14). We have analyzed air pollutant measurements in the Sao Paulo metropolitan area over the last 30 years, and observed that pollutant levels recorded at each station were highly correlated with one another.…”

“…In large cities, these small particles are the most harmful to human health, as they can induce pulmonary inflammation and oxidative stress, which in turn may stimulate specific transcription factors, such as nuclear factor kB, activator protein 1, chemokines, and other serum proinflammatory mediators (12). Some studies have demonstrated that exposure to high concentrations of pollutants is associated with an increased level of serum inflammatory markers in children (13,14).…”