T lymphocyte-proliferative responses of harbor seal (Phoca vitulina) peripheral blood mononuclear cells (PBMCs) exposed to pharmaceuticals in vitro

• Published in: Marine pollution bulletin 2018-02, Vol.127, p.225-234
• Main Authors: Kleinert, Christine, Lacaze, Emilie, Fortier, Marlène, Hammill, Mike, De Guise, Sylvain, Fournier, Michel
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Additives; Animals; Aquatic environment; Binary mixtures; Bioaccumulation; Blood; Carbamazepine; Carbamazepine - toxicity; Cell Proliferation; Cell Proliferation - drug effects; Drugs; Erythromycin; Erythromycin - toxicity; Ethinyl Estradiol; Ethinyl Estradiol - toxicity; Ethinylestradiol; Exposure; Female; Immune response; Immunotoxicity; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Life Sciences; Lymphocytes; Lymphocytes T; Male; Marine mammal; Marine mammals; Naproxen; Naproxen - toxicity; Peripheral blood mononuclear cells; Pharmaceuticals; Phoca; Phoca - blood; Phoca vitulina; Proliferation; Seals; Sensitivity; Sex hormones; T-Lymphocytes; T-Lymphocytes - drug effects; Toxicity; Trophic levels; Water Pollutants, Chemical; Water Pollutants, Chemical - toxicity; Xenobiotics
• ISSN: 0025-326X; 1879-3363
• DOI: 10.1016/j.marpolbul.2017.12.001

The ubiquity of pharmaceuticals in the aquatic environment and the accumulation in organisms of lower trophic levels have been documented. The immunotoxicity of these xenobiotics has however been little investigated. This study assessed the effects of pharmaceuticals on the immune responses of harbor seal lymphocytes. Peripheral blood mononuclear cells isolated from harbor seal pups were exposed to varying concentrations of 17α-ethinyl estradiol (250–50,000μg/L), naproxen (500–100,000μg/L), carbamazepine (500–100,000μg/L), erythromycin (750–150,000μg/L) and binary mixtures thereof in vitro. All individual compounds and mixtures inhibited lymphocyte proliferation. Mixture effects were non-additive and predictive values overestimated the inhibition of proliferation. Male pups were more sensitive to erythromycin exposure. Comparison with the sensitivity of the 11B7501 cell line showed a higher sensitivity of pups to individual compounds and the inverse trend for mixtures. Based on our results, we hypothesize that pharmaceuticals may have the potential to interrupt immune functions in harbor seals. •First study to measure toxicity of pharmaceuticals in marine mammal primary cells.•17a-ethinyl estradiol, naproxen, erythromycin and carbamazepine suppressed harbor seal T cell proliferation.•Mixtures had non-additive effects on lymphocyte proliferation.•Male seal lymphocytes demonstrated a greater inhibition of proliferation to antibiotic erythromycin.