| In Vitro Activation of Cord Blood Mononuclear Cells and Cytokine Production in a Remote Coastal Population Exposed to Organochlorines and Methyl Mercury Houda Bilrha,1 Raynald Roy,1 Brigitte Moreau,1 Marthe Belles-Isles,1 Éric Dewailly,2 and Pierre Ayotte2
1Rheumatology-Immunology Research Unit, and 2Department of Social and Preventive Medicine, CHUQ-Laval University Medical Center, Québec City, Québec, Canada 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- (TNF-) secretion and plasma PCB, p,p´-DDE, and HCB concentrations (p < 0.05) . Our data support a negative association between TNF- secretion by CBMCs and prenatal organochlorine exposure. If the relationship between organochlorine and TNF- 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. Key words: Canada, cytokines, immune system, maternal exposure, methyl mercury, neonate, organochlorine insecticides, polychlorinated biphenyls. Environ Health Perspect 111:1952-1957 (2003) . doi:10.1289/ehp.6433 available via http://dx.doi.org/ [Online 29 August 2003]
Address correspondence to P. Ayotte, Public Health Research Unit, CHUQ-CHUL, 945 avenue Wolfe, Québec City, Québec, Canada G1V 5B3. Telephone: (418) 650-5115 ext. 4654. Fax: (418) 654-2148. E-mail: pierre.ayotte@inspq.qc.ca We gratefully acknowledge the support of M. Daris, C. Girardin, and M. Simard as well as the nursing staff from the Perinatal Unit of Sept-Îles Hospital, particularly C. Albert and R. Bélanger. Many thanks to N. Gauthier for coordinating the work at Sept-Îles Hospital and to S. Gingras for the statistical analyses. This study was funded by the Joint Programme FRSQ-PNRDS-Saint-Laurent Vision 2000 (960875-104) and the Canadian Network of Toxicology Centres. The authors declare they have no competing financial interests. Received 1 May 2003 ; accepted 28 August 2003.
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