Developmental immunotoxicity in male rats after juvenile exposure to ethanol. 2013

Elisa C M Tonk, and Aart Verhoef, and Eric R Gremmer, and Henk van Loveren, and Aldert H Piersma
Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands. ilse.tonk@rivm.nl

The aim of the present study was to determine the sensitivity of the developing immune system to ethanol (EtOH) after exposure from postnatal day (PND) 10 onward. Adult Wistar dams and litters were exposed to EtOH via drinking water (0, 0.25, 1.5, 2.75, 4, 5.25, or 6.5% (w/v) EtOH ad libitum) and drinking water exposure of the F1 was continued from weaning until sacrifice. Immune assessments were performed at postnatal days (PNDs) 21, 42, and 70. Furthermore, Keyhole Limpet Hemocyanin (KLH) specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35. EtOH exposure affected innate immune responses, such as LPS-induced NO-production by adherent splenocytes, as well as adaptive immune responses as represented by KLH-specific parameters. The most sensitive developmental parameters included effects on maternal and pup bodyweight with calculated BMDs of 4.0% and 4.3% EtOH, respectively. The most sensitive immune parameters were affected at dose levels lower than those affecting developmental parameters and included KLH-specific immune responses, LPS-induced NO production by adherent splenocytes, and IL-10 production by ConA stimulated splenocytes. Calculated BMDs for these parameters were between 0.01% and 0.1% EtOH. A comparison of the results of this juvenile study with an extended one-generation reproductive toxicity study revealed that the juvenile study design may result in a higher sensitivity related to differences in the exposure design. These findings demonstrate the relative sensitivity of the developing immune system for EtOH exposure, the additional value of assessing functional immune parameters, and the importance of the juvenile window in developmental immunotoxicity testing.

UI MeSH Term Description Entries
D007111 Immunity, Cellular Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Cell-Mediated Immunity,Cellular Immune Response,Cell Mediated Immunity,Cell-Mediated Immunities,Cellular Immune Responses,Cellular Immunities,Cellular Immunity,Immune Response, Cellular,Immune Responses, Cellular,Immunities, Cell-Mediated,Immunities, Cellular,Immunity, Cell-Mediated,Response, Cellular Immune
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D005260 Female Females
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor

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