Restricted growth before birth enhances allergenic immune responses in adolescent sheep (#89)
Background: Prenatal exposures including maternal diet can alter immune function after birth. Preterm birth is associated with altered immune function in childhood1 and increased risk of asthma2. Low birth-weight impairs immune responses following vaccination in children and adolescents3. It is unclear whether this reflects down-regulation of the immune system as a whole, or a shift from Type 1 (immunity) to Type 2 (allergic) immune responses following intrauterine growth-restriction (IUGR).
Methods: Intrauterine growth was restricted by surgical removal of most placental implantation sites from the uterus of sheep prior to mating. Spontaneous restriction also occurred due to twinning. Lambs from unoperated ewes (CON, 26 twins, 9 singletons) and placentally-restricted ewes (PR, 12 twins, 12 singletons) were sensitised to ovalbumin (OVA) and house dust mite allergen (HDM) in alum by 4 fortnightly injections from 20 weeks of age4. Circulating immunoglobulins (Ig) were measured by ELISA in sera collected at baseline and 14 days after the last injection; cellular immune responses were assessed at 28 weeks by cutaneous allergen challenge4. Effects of PR and birth-weight were analysed by χ2 and ANOVA.
Results: Placental restriction reduced birth-weight (Figure A) by 11% overall (P=0.032) and by 23% in singleton lambs (P=0.003). HDM-specific IgE responses were greater (P=0.010) and OVA-specific total Ig responses tended to be greater (P=0.061) in PR than CON lambs (Figure B). Overall, late-phase cutaneous reactions to HDM tended to occur less frequently in light birth-weight lambs than those of heavier birth-weights (P=0.067), and in singletons, late phase cutaneous reactions to OVA occurred less frequently in PR than CON lambs (Figure C, P=0.008).
Conclusions: Increased IgE responses to HDM and decreased late-phase cutaneous reactivity in PR and/or low birth-weight lambs, together with impaired response to vaccination in IUGR humans, suggests IUGR may shift immune responses from Type 1 to Type 2.
- Buske-Kirschbaum A et al. Hypothalamic-pituitary-adrenal axis function and the cellular immune response in former preterm children. J Clin Endocrinol Metab 92: 3429-35, 2007.
- Jaakkola JJ et al. Preterm delivery and asthma: a systematic review and meta-analysis. J Allergy Clin Immunol 118: 823-30, 2006.
- McDade TW et al. Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr 74: 543-8, 2001.
- Bischof R et al. Immune response to allergens in sheep sensitized to house dust mite. Journal of Inflammation 5: 16, 2008.