Arsenic exposure associated T cell proliferation, smoking, and vitamin D in Bangladeshi men and women

Abstract

There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (t20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men,

Exposure to arsenic and level of Vitamin D influence the number of Th17 cells and production of IL-17A in human peripheral blood mononuclear cells in adults

“…A list of 2,197 potential participants was generated from the Health Effects of As Longitudinal Study (HEALS) central database based on the following eligibility criteria [ 15 ]. Eligible participants were healthy men and women between the ages of 35 and 65 years, regardless of smoking status, and living in the study area of Araihazar, Bangladesh.…”

“…All samples were analyzed at the end of the study and researchers were blinded to the exposure. As described previously [ 15 ], samples were thawed quickly in a 37°C water bath, washed with warmed media, resuspended in 3 ml fresh media and counted. Cell counts and viabilities were acquired with a Nexcelom Cellometer Auto 2000 Cell Viability Counter using acridine orange and propidium iodide (AO/PI; Nexcelom Bioscience, CS2-0106) according to manufacturer’s directions.…”

“…Sample serums were sent to the Department of Medicine in Columbia University’s Medical Center for determination of VitD levels. 25-hydroxyvitamine D, the sum of 25-hydroxyvitamine D2 (25(OH)D 2 ) and 25-hydroxyvitamine D (25(OH)D 3 ), were assayed by Ultra-Performance Liquid Chromatography- tandem mass spectrometry (LC-MS/MS) as described previously [ 15 ]. The level of sensitivity for LC-MS/MS assay was 1.0 ng/ml for both 25(OH)D 2 and 25(OH)D 3 .…”

“…We previously found that As and environmental polycyclic aromatic hydrocarbons (PAHs) modulate lymphocyte subsets and cytokines in male smokers and non-smokers [ 14 ]. Recently we found that VitD plays a significant role in modulating the activation and proliferation of T-cells in As–exposed PBMC obtained from non-smoking and smoking men [ 15 ].…”

“…We and others find a high incidence of VitD deficiency in Bangladesh [ 17 ]. Therefore, a second goal of these studies was to follow-up on our observations that VitD may modulate As immunotoxicity [ 15 ]. VitD deficiencies are associated with cancer and immunosuppression in human populations [ 18 ].…”