title: Arsenic exposure and cell-mediated immunity in pre-school children in rural Bangladesh.
abstract: Prenatal arsenic exposure has been associated with reduced thymic index and increased morbidity in infants, indicating arsenic-related impaired immune function. We aimed at elucidating potential effects of pre- and postnatal arsenic exposure on cell-mediated immune function in pre-school aged children. Children born in a prospective mother-child cohort in rural Bangladesh were followed up at 4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of arsenic metabolites (U-As) in child urine and maternal urine during pregnancy, using high-performance liquid chromatography online with inductively coupled plasma mass spectrometry. For assessment of delayed type hypersensitivity response, an intradermal injection of purified protein derivative (PPD) was given to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration was measured after 48-72 h. Plasma concentrations of 27 cytokines were analyzed by a multiplex cytokine assay. Children's concurrent, but not prenatal, arsenic exposure was associated with a weaker response to the injected PPD. The risk ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126-1228 μg/l), compared with the lowest (range 12-34 μg/l). The p for trend across the quartiles was 0.003. The association was stronger in undernourished children. Children's U-As in tertiles was inversely associated with two out of 27 cytokines only, i.e., IL-2 and TNF-α, both Th1 cytokines (in the highest tertile, regression coefficients (95% CI): -1.57 (-2.56, -0.57) and -4.53 (-8.62, -0.42), respectively), but not with Th2 cytokines. These associations were particularly strong in children with recent infections. In conclusion, elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Centre for Vaccine Sciences, International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors.forename: Sultan
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London, UK, and MRC Keneba, The Gambia.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Kippler
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Renee
authors.initials: R
authors.lastname: Gardner
authors.affiliation: Centre for Vaccine Sciences, International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: M D H
authors.initials: MD
authors.lastname: Hawlader
authors.affiliation: Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Wagatsuma
authors.affiliation: Centre for Vaccine Sciences, International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden marie.vahter@ki.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Vahter
mesh_terms: D001151:Arsenic / Q000097:blood / Q000633:toxicity* / Q000652:urine; D001459:Bangladesh; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity* / Q000652:urine; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000276:immunology; D011446:Prospective Studies; D012424:Rural Population; D013054:Spectrophotometry, Atomic
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D001151:Arsenic
keywords: arsenic exposure; cell-mediated immunity; delayed type hypersensitivity; immunotoxicity