Longitudinal effect of phthalates exposure on allergic diseases in children.

BACKGROUND: Environmental chemicals, such as phthalates, phenols, and parabens, may affect children's immune development and contribute to the risk of atopic diseases and asthma. OBJECTIVE: To evaluate the associations between prenatal and childhood phthalate exposure and atopic diseases in children at the age of 9 years. METHODS: This analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child Cohort Study. Phthalate metabolite levels were assessed in the urine samples collected from mothers during the third trimester of pregnancy and from children at age of 2 and 9 years. For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical record of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. RESULTS: A higher urine concentration of mono-2-ethyl-5-oxohexyl phthalate increased the risk of food allergy in children at the age of 9 years (odds ratio [OR], 1.75; 95% CI, 1.19-2.57; P = .004) and decreased the risk of atopic dermatitis (OR, 0.49; 95% CI, 0.27-0.87; P = .02). For mono-2-ethyl-5-hydroxyhexyl phthalate, an increased risk of atopic dermatitis was observed (OR, 1.90; 95% CI, 1.18-3.05; P = .008). A higher urine concentration of mono-benzyl phthalate increased the risk of asthma in children (OR, 1.67; 95% CI, 1.08-2.58; P = .02), but the risk of asthma decreased when the concentration of mono-2-ethylhexyl phthalate was higher (OR, 0.64; 95% CI, 10.43-0.97; P = .04). CONCLUSION: Our study has not provided clear evidence of the negative effect of phthalate exposure during pregnancy and within the 9 years after birth on allergic diseases in children.

Mannosylated lipoarabinomannan balances apoptosis and inflammatory state in mycobacteria-infected and uninfected bystander macrophages.

To assess the role of mannosylated lipoarabinomannan (ManLAM) in the inflammatory and apoptotic response of mycobacteria-infected and uninfected, bystander cells we applied a mouse macrophage model of infection with avirulent strains--Mycobacterium bovis BCG, Mycobacterium tuberculosis (MTB) H37Ra and compared with a virulent MTB H37Rv strain infection. ManLAM contributed to the infection of macrophages by protection from apoptosis with stabilized Bcl-2 expression and down-regulated Bax expression for infected cells (BCG) or with stabilized Bcl-2 expression for uninfected bystander target cells (H37Ra). Additionally, ManLAM up-regulated FasL expression on the infected cells. Active extracellular signal-regulated kinase (ERK1/2) in BCG and H37Rv infection provided an anti-apoptotic effect by stabilization of anti-apoptotic Bcl-2 expression in the infected cells. Inhibitors specific for c-Jun-NH2-terminal kinase or stress-activated kinase (JNK) and p38 kinase decreased apoptosis of infected cells (BCG, H37Ra) and of uninfected bystanders (H37Ra) by down-regulating Bax. ManLAM significantly down-regulated production of pro-inflammatory IL-12 and TNF-alpha and activation of JNK by both avirulent strains. We conclude that by stabilization of Bcl-2 expression, down-regulation of JNK activity and down-regulation of pro-inflammatory cytokines production ManLAM can contribute to suppression of apoptosis and inflammatory reaction of uninfected, bystander cells.