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

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 (Quebec, 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 (CD(4+)CD45RO(+), CD(8+)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-alpha (TNF-alpha) secretion and plasma PCB, pp'-DDE, and HCB concentrations (p < 0.05). Our data support a negative association between TNF-alpha secretion by CBMCs and prenatal organochlorine exposure. If the relationship between organochlorine and TNF-alpha 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.