Second generation effects of maternal ethanol consumption on immunity to Trichinella spiralis in female rats.

Abstract

The deleterious effects of maternal ethanol consumption on neonatal immune development and early immune responses has been well documented. However, the effects of such neonatal exposure to maternally consumed ethanol on the neonates' immune responses in their adult life, especially in combination with additional ethanol exposure, has received little attention. For these experiments, female rats were fed on either 6% ethanol or pair-fed isocaloric control Lieber-DeCarli liquid diets for 30 days prior to, and during, pregnancy and lactation. One day after weaning their pups, the mothers were infected with 1000 Trichinella spiralis larvae, and maintained on diets for an additional 20 days. At this time, they were challenged with 2000 T. spiralis larvae, killed 3 days later, and their immune status determined. These animals served as the first generation alcohol animals. Their female offspring served as the experimental second generation animals. These animals received maternal ethanol during pregnancy and lactation and control diet during their juvenile period (from weaning to 90 days of age). They were then subjected to a schedule of ethanol or pairfeeding, identical to the first generation dams. Two groups of second generation animals were established: Group 1 was exposed to ethanol during their dam's pregnancy and lactation periods only, with no subsequent ethanol treatment; Group 2 received ethanol during their dam's pregnancy and lactation periods and then again throughout their adult experimental period. Our previous studies showed only minimal changes following a secondary challenge in T. spiralis-immunized rats; however, neonates born to alcohol-consuming mothers did show some depressed secondary immune responses when challenged soon after weaning. We chose to use a secondary immune challenge to assess further immune alterations in second generation adult animals. No differences between any of the ethanol and pair-fed groups were observed in intestinal worm burdens, which is similar to data previously reported for adult alcohol-consuming animals. However, second generation group 2 animals demonstrated significantly reduced proliferation responses to T. spiralis antigen and Concanavalin A (Con A) stimulation relative to the ethanol first generation and to the second generation Group 1 animals. This group also demonstrated significantly lower absorbencies in the ELISA assay for specific IgM and IgG anti-T. spiralis antibodies than the pair-fed, ethanol first and second generation Group 1 animals. The proportion of total T cells and cytotoxic T cells was significantly lower and the proportion of natural killer cells was elevated in both second generation ethanol Groups 1 and 2 relative to the ethanol first generation and pair-fed groups. In addition, Group 2 second generation animals showed significantly lower proportions of total leukocytes and T cells than Group 1 second generation animals. Although secondary immune responses to T. spiralis infection were not altered in rats exposed to ethanol only as adults, exposure to maternal ethanol does affect some specific immune responses in second generation adult life and maternal exposure may exert cumulative immune effects in concert with later consumption of ethanol by offspring born to alcoholic mothers.