Assessment of arsenic and polycyclic aromatic hydrocarbon (PAH) exposures on immune function among males in Bangladesh

Abstract

Arsenic and polycyclic aromatic hydrocarbons (PAH) are environmental pollutants to which people around the world are exposed through water, food and air. In mouse and in vitro studies of human cells, both of these chemicals have been shown to modulate the immune system. In some experimental studies, a synergistic disruption of immune function was observed by a combined exposure to arsenic and PAH. However, a joint effect of arsenic and PAH on immune function has not been studied in humans. We have conducted an epidemiological investigation to examine effects of chronic arsenic and PAH exposures on immune function. We assessed T-cell proliferation (TCP) and cytokine production of anti-CD3/anti-CD28 stimulated lymphocytes in human peripheral blood mononuclear cells (HPBMC) among 197 healthy men enrolled to the Health Effects of Arsenic Longitudinal (HEALS) cohort in Bangladesh. By design, approximately half were active smokers and the rest were never smokers. Our analyses demonstrated that IL-1b, IL-2, IL-4 and IL-6 were significantly stimulated as a function of urinary arsenic levels in models adjusted for age, body mass index (BMI), smoking status and PAH-DNA adducts. After correcting for false detection rate (FDR), only IL-1b remained statistically significant. We found a U-shaped dose response relationship between urinary arsenic and IL-1b. On the other hand, PAH-DNA adducts were associated with an inhibition of TCP and appeared as an inverted U-shape curve. Dose response curves were non-monotonic for PAH-DNA adduct exposures and suggested that cytokine secretion of IFNg, IL-1b, IL-2, IL-10 and IL17A followed a complex pattern. In the majority of donors, there was a trend towards a decrease in cytokine associated with PAH-DNA adducts. We did not observe any interaction between urinary arsenic and PAH-DNA adducts on immune parameters. Our results indicate that long-term exposures to arsenic and PAH have independent, non-monotonic associations with TCP and cytokine production.

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

“…Various measures of adaptive immunity [7,10,[18][19][20][21] and innate immunity [22][23][24] are suppressed by arsenic exposure. TCP is critical for cell activation, effector, and helper cell functions [25].…”

“…Urine samples (15 ml) were collected at the study clinic at Araihazar, Bangladesh. Total arsenic in urine was accessed by graphite furnace atomic-absorption spectrophotometry (GFAAS) as previously described [7,8]. Urinary creatinine, quantified by a colorimetric method based on the Jaffe reaction, was used to correct urinary arsenic (UAs) and metabolites.…”

“…A standard mitogenesis assay using tritiated (3H) thymidine previously described [7] was used to access T lymphocyte proliferation. Briefly, cells were plated into six replicate wells at 1x10 5 cells/wells (for each mitogen) in a 96 well, flat bottom tissue culture plates.…”

“…Previous work from our labs has shown that arsenic modulates various immune functions measured in cryopreserved peripheral blood mononuclear cells (PBMC) obtained from men chronically exposed to arsenic in Bangladesh [7,8]. Those studies were limited to 181 males equally divided between smokers and never smokers as well as low and high arsenic exposure.…”

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

“…One of the bacteria negatively associated with serum uric acid, F. prausnitzii , has been reported to encode a methyltransferase for arsenic detoxification (Supplementary Table 3i) 24 . IL-1β, the major cytokine responsible for gout 68 , has been associated with urinary level of arsenic 69 . Co-stimulation of patient-derived PBMCs with monosodiurm urate crystals and TLR2 or TLR4 (toll-like receptors) ligands have been shown to disrupt IL-1β/ IL-1Ra (IL1 receptor antagonist) balance 70 , consistent with involvement of microbes in gout.…”