Effects of maternal ethanol consumption on the subsequent development of immunity to Trichinella spiralis in rat neonates.

Abstract

The immune response of rat pups to the intestinal parasite Trichinella spiralis was studied to determine if maternal pre- and/or postnatal ethanol consumption affected neonatal immune responses. Female rats were fed ethanol-containing (36% of calories) or pair-fed control liquid diets and include groups that were maintained on ethanol as follows: group 1, from day 1 of pregnancy through weaning and whose pups were then placed on ethanol to sacrifice; group 2, from day 1 of pregnancy through lactation; group 3, from day 1 of pregnancy through pup delivery; and group 4, from day 1 of lactation through weaning. A parallel group of animals was pair-fed isocaloric control diet until sacrifice. The pups of all litters were immunized orally with 500 L1 (T. spiralis) larva 5 days after weaning. To examine the effects of maternal ethanol on primary immune responses, one-fourth of the pups from each litter were sacrificed on days 10 and 20 after immunization. To examine the effects on neonatal secondary immune responses, the remaining pups were challenged with 1,000 larva 30 days after the initial immunization and sacrificed either 3 or 8 days after challenge. At the time of sacrifice, blood samples were collected, the intestine removed to determine T. spiralis worm burdens, and suspensions of mesenteric lymph node (MLN) cells prepared. Intestinal worm counts and serum levels of anti-T. spiralis IgM and IgG antibodies, interleukin-2 (IL-2), and tumor necrosis factor (TNF) were determined. In vitro proliferation responses of MLN cells to T. spiralis antigen and to the mitogen concanavalin A (Con A) were also examined. Pups from groups 1 to 3 demonstrated significantly higher intestinal worm counts (decreased immunity) than the pair-fed controls at the day 20 primary immune response sacrifice, and pups from group 1 had significantly higher worm counts at day 3 after a secondary immune challenge. Pups of dams from groups 1, 3, and 4 had significantly lower IgM antibody titers at the day 20 primary immune response sacrifice. All experimental ethanol groups (1 to 4) demonstrated significantly lower IgG antibody titers than that observed in pair-fed control pups at the 20-day sacrifice. IgM antibody titers showed significant reductions for ethanol-treated groups at 3 and 8 days after T. spiralis secondary challenge. In addition, IgG antibody titers were also significantly reduced for all alcohol groups at 3 and 8 days during the secondary immune response. Serum IL-2 and TNF levels were significantly lower in all experimental ethanol groups (1 to 4) relative to pair-fed controls at day 20 during a primary immune response, and IL-2 levels at 3 days postchallenge were lower in groups 2 to 4 after a secondary immune challenge. MLN proliferation responses to antigen and Con A were significantly reduced in ethanol groups 1 to 3 and to Con A in group 4 at day 10 after a primary immune challenge. Ethanol group 3 pups also demonstrated a reduced response to antigen at day 20. For animals undergoing a secondary immune response, ethanol group 2 demonstrated a reduced response to antigen at day 3, whereas groups 2 and 4 showed increased reactivity to antigen at days 3 and 8 postchallenge. These results show that maternal ethanol consumption diminishes the capacity of neonates to respond to T. spiralis antigen and that the depressed immune response involves T- and B-cell-mediated reactions and also affects the production of certain cytokines. These results also suggest that the diminished immune responses are increased with longer periods of maternal and neonatal exposure to ethanol.