Lead and Immune Function

The heavy metal lead is a widely deposited environmental toxicant known to impact numerous physiological systems, including the reproductive, neurological, hepatic, renal, and immune systems. Studies illustrating the capacity of lead to impair immune function and/or host resistance to disease date back to at least the 1960s. However, it has only been in recent years that lead has been recognized among a new category of immunotoxicants—those that dramatically shift immune functional capacity while producing only modest changes to immune cell populations and lymphoid organs. These relatively noncytotoxic immunomodulating chemicals and drugs represent the immunotoxic hazards most difficult to identify and problematic for risk assessment using historic approaches. As a result, such environmental factors are also among the most likely to contribute to chronic immune-related disease at relevant exposure levels. This review considers the animal and human evidence that lead exposure can produce a stark shift in immune functional capacity with a skewing predicted to elevate the risk of atopic and certain autoimmune diseases. At the same time, host defenses against infectious agents and cancer may be reduced. Age-based exposure studies also suggest that levels of blood lead previously thought to be safe, that is, below 10 μg/dl, may be associated with later life immune alterations.     

Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial Growth Factor and Interleukin-5 in Atopic Children

Purpose

Previous studies have outlined mechanisms by which Mycoplasma pneumonia (M. pneumonia) infection may promote allergic lung inflammation and airway remodeling, and increasing evidence from human studies suggests that atypical bacterial infections contribute to asthma exacerbation, chronic asthma, and disease severity with changes in cytokine expression. The present study evaluated changes in serum levels of vascular endothelial growth factor (VEGF) and interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia.

Methods

We recruited a total of 72 children with pneumonia. The patients were divided into 4 groups: atopic children with M. pneumonia pneumonia (group I, n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic children with viral pneumonia (group III, n=13), and non-atopic children with viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor necrosis factor-α were measured at admission and at recovery using enzyme-linked immunosorbent assays.

Results

Serum levels of VEGF and IL-5 were elevated in group I compared with the other groups at both admission phase and clinical recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery phase than at admission phase (VEGF: 1,102.2±569.4 vs. 874.9±589.9 pg/mL, respectively; IL-5: 150.5±63.9 vs. 120.2±46.7 pg/mL, respectively).

Conclusions

The serum levels of VEGF and IL-5 were more increased in atopic children with M. pneumonia pneumonia than in the other groups. In this group, the serum levels of VEGF and IL-5 were more increased at recovery phase than at admission phase. The results of this study suggest that increases in VEGF and IL-5 may contribute to the development of hypersensitivity during M. pneumonia infection. These cytokines may act through their respective pro-inflammatory pathways to aggravate the allergic status and induce airway hypersensitivity during M. pneumonia pneumonia in atopic children.     

Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: a prospective prebirth cohort study

Background

Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines.

Objectives

The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood.

Material and methods

The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child’s gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts.

Results and conclusion

In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21−4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.     

Inhalant allergen sensitization is an independent risk factor for the development of angioedema

Background/objective

The etiology and risk factors for angioedema remain poorly understood with causative triggers often going undiagnosed despite repeated reactions. The purpose of this study was to determine the relationship between inhalant allergen sensitization and angioedema.

Association analysis of interleukin 5 receptor alpha subunit (IL5RA) polymorphisms and asthma

The alpha subunit of interleukin 5 receptor (IL5RA) on chromosome 3p26-p24 is known to regulate the development and function of eosinophils. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we investigated the genetic polymorphisms in IL5RA to evaluate the gene as a potential candidate for a host genetic study of asthma. By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within exons and flanking regions including a 1.5-kb promoter region of IL5RA; 10 common polymorphic sites were selected for genotyping in our asthma cohort (n=587). Two haplotype blocks were identified in a Korean population. Statistical analysis revealed that one promoter SNP, c.-5993A>G, and one ins/del polymorphism in intron 3, c.-480_482insdelGTT, showed significant association with the risk of asthma development. The genetic effects of c.-5993A>G and c.-480_482insdelGTT on asthma were more apparent among atopic subjects. Our findings suggest that polymorphisms in IL5RA might be among the genetic risk factors for asthma development, especially in atopic populations. IL5RA variant/haplotype information identified in this study will provide valuable information for strategies for the control of asthma.Electronic Supplementary Material Supplementary material is available for this article at     

Eosinophilic ascites: A diagnostic and therapeutic challenge

Eosinophilic gastroenteritis(EGE) is a rare condition characterized by eosinophilic infiltration of the gastrointestinal tract. Depending on the dominant layer of infiltration it is classified into three types namely, mucosal, muscularis and subserosal. The most uncommon variant is the subserosal type characterized by primarily subserosal disease, eosinophilic ascites and peripheral hypereosinophilia. The clinical features are non-specific with history of atopic predisposition and allergy. Endoscopic biopsy is frequently non-diagnostic due to an uninvolved gastrointestinal mucosa rendering its diagnosis a challenge. The mainstay of diagnosis is peripheral hypereosinophilia and eosinophil-rich ascitic fluid on diagnostic paracentesis. Oral steroid therapy is usually the first line of treatment with dramatic response. Due to a propensity for relapse, steroid-sparing therapy should be considered for relapses of EGE. We report a case of subserosal EGE with diagnostic clinical features and treatment response and review the current strategy in the management of eosinophilic ascites.     

Epidemiology of allergy

Atopic disease represents a spectrum of disorders characterized by abnormal sensitivity mediated by IgE; approximately 20% of Americans suffer from some form of allergic disease. The sequelae of inhalant and food allergies may present in many organ systems. Manifestations of allergic disease in one site are often associated with symptoms from another site. It is important for clinicians to understand the epidemiology of atopic disease and its causes to facilitate implementation of effective treatment and prevention strategies. This review focuses on the epidemiology of inhalant allergies causing allergic rhinitis and asthma and on IgE-mediated food allergies.