The aims of the present study were to assess whether protection against peanut (PN) sensitization can be conferred by maternal PN consumption alone and if so, whether protection was increased by mucosal adjuvant co-administration. lower PN-specific IgE levels and reduced PN-stimulated splenocyte and MLN cells cytokine secretion than offspring of non PN fed mothers. CT co-administration with PN enhanced these responses.. Milk from mothers fed PN and CT, but not PN alone preconceptionally and during pregnancy and lactation contained markedly and significantly increased levels of both peanut-specific IgG2a and IgA. Our study demonstrated that maternal feeding of PN alone had a protective effect against PN sensitization of the progeny, which was enhanced by co-administration of a mucosal adjuvant. Increased levels of PN-specific IgG2a and/or IgA in milk were seen when PN and CT were administered together, suggesting that transmission of maternal immunoglobulins may play a role in the observed protection. environment may strongly influence a childs immune system (Hubeau, Apostolou & Kobzik, 2006; Prescott et al., 1998). Maternal avoidance of PN during pregnancy and lactation was recommended for many years in the U.S. and the U.K. Recently, this recommendation has been revised due to lack of conclusive evidence of benefit (Greer, Sicherer, & Burks, 2008) and concerns that this approach may indeed increase the risk of development of PNA (Burks, 2008). Hourihane et al (2007) reported Cerovive PNA outcomes in a cohort of children born after the U.K. governments advice to mothers of high-risk infants to follow maternal avoidance during pregnancy and lactation, and to avoid introduction of PN to their children until 3 years of age. The rate of PNA in this cohort was 1.8%, the highest recorded at that time. In addition, several recent studies indicated that early introduction of PN to infants may be beneficial (Burks, 2008; Wennergren, 2009). The latest epidemiologic data suggests that earlier, more frequent and larger consumption of PN during the first year of life was Cerovive associated with a low prevalence of PNA as seen in Jewish Israeli children (0.17%) compared to Jewish children in the U.K. (1.85%) (du Toit et al., 2008). In the U.K., avoidance of PN was significantly more common in mothers during breastfeeding than in Israel, and avoidance during pregnancy had a similar trend. These findings raise the question whether introduction of PN during infancy, or even antenatally might be associated with development of tolerance to PN. Several rodent studies found that maternal exposure to certain allergens during pregnancy and lactation prevented offspring from developing allergic asthma (Fusaro et al., 2007; Polte, Hennig, & Hansen, 2008; Verhasselt et al., 2008). Although most of these studies employed ovalbumin (OVA) together with an adjuvant, one study showed that preconceptional feeding of OVA alone significantly prevented OVA-induced allergic airway response in the offspring, which was associated with maternal transmission of IgG (Hennig, & Hansen, 2008). However, a recent study showed that co-administration of the adjuvants pertussis toxin or aluminum hydroxide was required to protect offspring against OVA sensitization (Ellertsen, Nygaard, Melkild & Lovik, 2010). We previously reported that 5 week old offspring of PN-sensitized mothers exhibited IgG1-mediated anaphylaxis upon first exposure to PN, which was prevented by maternal ingestion of PN co-administered with CT at doses below the clinical threshold (induction of symptoms) throughout pregnancy and lactation (Lopez-Exposito, Song, Jarvinen, Srivastava & Li, 2009). Protected offspring had higher levels of protective PN-specific IgG2a antibody and lower PN-specific IgG1 to IgG2a ratios than unprotected offspring that reflected maternal serum concentrations. We also found that offspring of mothers fed PN with CT throughout pregnancy and lactation showed significantly reduced PN-IgE production in response to 6 weeks of sensitization (Lopez-Exposito, Song, Jarvinen, Srivastava & Li, 2009). However, whether maternal feeding of PN alone can prevent offspring from PN sensitization was not investigated. LIPH antibody The mechanisms underlying the protection induced by maternal dietary PN exposure against PN sensitization in the progeny also remain unknown. The objective of this study was to assess whether maternal feeding of PN alone protects against PN Cerovive active sensitization in offspring compared to the effect of a mucosal adjuvant co-administration with PN in mothers who are PN-allergic or PN-immunized. In this study, the potential protective Cerovive role of PN-specific antibodies transferred from mothers to offspring is also discussed. 2. Materials and Methods 2.1 Animals and reagents Six-week-old female and male C3H/HeJ mice purchased from the Jackson Laboratory (Bar Harbor, ME) were maintained on PN-free chow under specific pathogen-free conditions.