Ll. Seelig et al., EFFECTS OF MATERNAL ETHANOL-CONSUMPTION ON THE SUBSEQUENT DEVELOPMENTOF IMMUNITY TO TRICHINELLA-SPIRALIS IN RAT NEONATES, Alcoholism, clinical and experimental research, 20(3), 1996, pp. 514-522
The immune response of rat pups to the intestinal parasite Trichinella
spiralis was studied to determine if maternal pre- and/or postnatal e
thanol consumption affected neonatal immune responses. Female rats wer
e fed ethanol-containing (36% of calories) or pair-fed control liquid
diets and include groups that were maintained on ethanol as follows: g
roup 1, from day 1 of pregnancy through weaning and whose pups were th
en placed on ethanol to sacrifice; group 2, from day 1 of pregnancy th
rough lactation; group 3, from day 1 of pregnancy through pup delivery
; and group 4, from day 1 of lactation through weaning. A parallel gro
up of animals was pair-fed isocaloric control diet until sacrifice. Th
e pups of all litters were immunized orally with 500 L(1) (T. spiralis
) larva 5 days after weaning. To examine the effects of maternal ethan
ol on primary immune responses, one-fourth of the pups from each litte
r were sacrificed on days 10 and 20 after immunization. To examine the
effects on neonatal secondary immune responses, the remaining pups we
re challenged with 1,000 larva 30 days after the initial immunization
and sacrificed either 3 or 8 days after challenge. At the time of sacr
ifice, blood samples were collected, the intestine removed to determin
e 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 nec
rosis factor (TNF) were determined. In vitro proliferation responses o
f MLN cells to T. spiralis antigen and to the mitogen concanavalin A (
Con A) were also examined. Pups from groups 1 to 3 demonstrated signif
icantly higher intestinal worm counts (decreased immunity) than the pa
ir-fed controls at the day 20 primary immune response sacrifice, and p
ups 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 r
esponse sacrifice. All experimental ethanol groups (1 to 4) demonstrat
ed significantly lower IgG antibody titers than that observed in pair-
fed control pups at the 20-day sacrifice. IgM antibody titers showed s
ignificant reductions for ethanol-treated groups at 3 and 8 days after
T. spiralis secondary challenge. In addition, IgG antibody titers wer
e also significantly reduced for all alcohol groups at 3 and 8 days du
ring the secondary immune response. Serum IL-2 and TNF levels were sig
nificantly lower in all experimental ethanol groups (1 to 4) relative
to pair-fed controls at day 20 during a primary immune response, and I
L-2 levels at 3 days postchallenge were lower in groups 2 to 4 after a
secondary immune challenge. MLN proliferation responses to antigen an
d 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 grou
p 3 pups also demonstrated a reduced response to antigen at day 20. Fo
r animals undergoing a secondary immune response, ethanol group 2 demo
nstrated 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 de
pressed immune response involves T- and B-cell-mediated reactions and
also affects the production of certain cytokines. These results also s
uggest that the diminished immune responses are increased with longer
periods of maternal and neonatal exposure to ethanol.