In vitro activation of cord blood mononuclear cells and cytokine production in a remote coastal population exposed to organochlorines and methyl mercury.

Abstract

Remote coastal populations that rely on seafood for subsistence often receive unusually high doses of organochlorines and methyl mercury. Immunosuppression resulting from prenatal exposure to organochlorines has been reported in wildlife species and humans. In this study, we assessed lymphocyte activation and associated cytokine secretion in 47 newborns from a remote maritime population living on the Mid and Lower North Shore regions of the St. Lawrence River (Québec, Canada; subsistence fishing group) and 65 newborns from nearby urban settings (reference group). Cord blood samples were collected for organochlorine and mercury analyses and also to isolate cord blood mononuclear cells (CBMCs) for the in vitro assessment of cytokine production and expression of surface markers after mitogenic stimulation (CD4 + CD45RO + , CD8 + CD45RO + , CD3 + CD25 + , and CD8 + HLA-DR + ). Blood mercury and plasma concentrations of polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p´-DDE), and hexachlorobenzene (HCB) were significantly higher in the subsistence fishing group than in the reference group (p < 0.001). No difference was observed between the two groups regarding subsets of lymphocytes showing markers of activation. In vitro secretion of cytokines by CBMCs after mitogenic stimulation was lower in the subsistence fishing group than in the reference group (p < 0.05). Moreover, we found an inverse correlation between tumor necrosis factor-α (TNF-α) secretion and plasma PCB, p,p´-DDE, and HCB concentrations (p < 0.05). Our data support a negative association between TNF-α secretion by CBMCs and prenatal organochlorine exposure. If the relationship between organochlorine and TNF-α secretion is causal, it would suggest a role for this important proinflammatory cytokine in mediating organochlorine-induced immunotoxicity in infants developmentally exposed to these compounds.

Correlation between maternal milk and infant serum levels of chlorinated pesticides (CP) and the impact of elevated CP on bleeding tendency and immune status in some infants in Egypt

“…For these studies, TNFα was selected as the representative pro-inflammatory, and IL-10 as the anti-inflammatory, cytokine for analysis in that each were previously monitored by Bilrha et al (2003) to investigate their association with prenatal exposure to some OC. Several other studies have monitored the impact of different pesticides on levels of these cytokines as well (see Duramad et al, 2007), but our study is the first performed on Egyptian infants.…”

“…Furthermore, O'Neill (2002) suggested that binding of dioxin-like compounds to the aryl hydrocarbon receptor (a transcription factor) can antagonize the effects of another transcription factor, nuclear factor (NF)-κB, an important regulator of immune and inflammatory gene expression (Sonne et al, 2006). Bilrha et al (2003) found that newborns exposed to OC in utero had significantly decreased TNFα production, suggesting that these children may be more susceptible to infection. These data indicate further that early exposures to environmental toxicants can directly impact the development and function of a child's immunity.…”

“…This has led to recognition of cytokine expression and secretion as a useful biomarker to assess the status and progression of a host immune response. Since then, numerous studies have used immune markers that include cytokine profiles to evaluate the effect of environmental toxicants such as volatile organic compounds, PCBs, and organochlorines on the immunity of children (Lehmann et al, 2002;Bilrha et al, 2003;ten Tusscher et al, 2003).…”

Predictors of adipose tissue concentrations of organochlorine pesticides in a general Danish population

“…Organochlorine pesticides are carcinogenic in animals (International Agency for Research on Cancer, 1987) and the immunotoxicity of selected organochlorine pesticides has been documented in vitro (Bilrha et al, 2003), in ovo (Lavoie and Grasman, 2007), as well as in animals (Bernhoft et al, 2000) and in human fetal, neonatal and infant immune systems (Repetto and Baliga, 1997;Dewailly et al, 2000;Heilmann et al, 2006). Concern about organochlorine pesticides as risk factors for cancer has prompted research into determinants of blood levels and adipose tissue concentrations of these compounds in the general population and a growing number of epidemiological studies have investigated blood or adipose levels of organochlorine pesticides and their metabolites in association with cancer, neurodevelopmental effects, immunotoxicity and reproductive outcomes (Longnecker et al, 1997;WHO, 2003).…”

Incidence Rates of Malignant Diseases in Childhood and Adolescence in Children to Swedish Fishermen

“…Concentrations of organochlorines were significantly higher in the subsistence fishing group. In vitro secretion of tumour necrosis factor-alpha correlated inversely with organochlorine concentration [34].…”