title: Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD.
abstract: While the immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well established, the effects of complex environmental mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) are poorly understood. Many PHAHs, including the polychlorinated-biphenyls (PCBs), -dibenzofurans (PCDFs), and dibenzo-p-dioxins (PCDDs), possess 'dioxin-like' activities, and accumulate in the aquatic food chain. Organisms occupying high trophic levels may therefore be exposed to concentrations which may present an immunotoxic risk. In this study, pregnant PVG rats were administered a daily oral dose of 1 ml of the following during pregnancy and lactation: (1) oil extracted from herring caught in the relatively uncontaminated Atlantic Ocean; (2) oil extracted from herring caught in the contaminated Blastic Sea; or (3) the Atlantic herring oil extract spiked with 2,3,7,8-TCDD. The daily intakes of aryl hydrocarbon (Ah)-receptor dependent toxic equivalents (TEQ) for mothers were 0.3 in the Atlantic group, 2.1 in the Baltic group, and 134 ng/kg body wt. in the 2,3,7,8-TCDD positive control group. Immune function and host resistance to rat cytomegalovirus (RCMV) were assessed in offspring aged 11, 25, 46 or 59 days. Rat pups in the positive control TCDD-spiked group exhibited immunosuppression characterized by reduced thymus weight and cellularity, reduced thymocyte and splenocyte proliferative responses to T-dependent mitogens in vitro, reduced virus-associated natural killer (NK) cell and specific antibody responses. While less pronounced, a similar pattern of effects was observed in the rat pups exposed only to the Baltic Sea herring oil. These immunotoxic effects were transient in both exposure groups, with a time-related recovery in immune function possibly due to the half-life of TCDD in rats and the waning exposure levels in the rapidly growing pups. We previously demonstrated that the same Baltic Sea herring led to impaired natural killer cell and T-lymphocyte function in harbour seals during the course of a long-term captive feeding study. The collective results of these studies in rats and seals indicate the immunotoxic potential of environmental mixtures at current levels in the aquatic environment, and suggest that the developing immune system of young mammals may be at particular risk.
authors.affiliation: Seal Rehabilitation and Research Centre, Pieterburen, The Netherlands.
authors.forename: P S
authors.initials: PS
authors.lastname: Ross
authors.forename: R L
authors.initials: RL
authors.lastname: de Swart
authors.forename: H
authors.initials: H
authors.lastname: van der Vliet
authors.forename: L
authors.initials: L
authors.lastname: Willemsen
authors.forename: A
authors.initials: A
authors.lastname: de Klerk
authors.forename: G
authors.initials: G
authors.lastname: van Amerongen
authors.forename: J
authors.initials: J
authors.lastname: Groen
authors.forename: A
authors.initials: A
authors.lastname: Brouwer
authors.forename: I
authors.initials: I
authors.lastname: Schipholt
authors.forename: D C
authors.initials: DC
authors.lastname: Morse
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
authors.forename: A D
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: J G
authors.initials: JG
authors.lastname: Vos
mesh_terms: D000818:Animals; D001454:Baltic States; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D005395:Fish Oils / Q000633:toxicity*; D005399:Fishes; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007107:Immune System / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013974:Thyroxine / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D005395:Fish Oils; D000072317:Polychlorinated Dibenzodioxins; D014874:Water Pollutants, Chemical; D013974:Thyroxine