Combined Supplementation with Arachidonic and Docosahexaenoic Acids in T Helper Type-2 Skewed Brown Norway Rat Offspring is Beneficial in the Induction of Oral Tolerance toward Ovalbumin and Immune System Development

Abstract

Background A T helper type-2 (Th2) skewed immune response is associated with food allergies. Docosahexaenoic (DHA) and arachidonic acid (ARA) have been shown to promote oral tolerance (OT) in healthy rodents. Objectives To study the effect of combined ARA + DHA supplementation during suckling and weaning period on OT and immune system development in Th2 skewed Brown Norway rat offspring. Methods Dams were fed ARA + DHA (0.45% ARA, 0.8% DHA w/w of total fat; n = 10) as suckling period diet (SPD) or control SPD (0% ARA, 0% DHA, n = 8). At 3-weeks, offspring from each SPD groups received ARA + DHA (0.5% ARA, 0.5% DHA w/w of total fat) weaning diet (WD) or control until 8 weeks. For OT, offspring were orally exposed to either, ovalbumin (Ova) or placebo between 21–25 days followed by systemic immunization with Ova + adjuvant at 7-week. Primary outcomes, ex-vivo cytokine production by splenocytes and plasma Ova-specific-immunoglobulins, were analysed using a 3-way ANOVA. Results At 8-week, despite no lasting effect of SPD on splenocytes fatty acids, ARA + DHA WD resulted in 2x higher DHA in splenocyte phospholipid compositions without affecting ARA. OT development was observed in Ova exposed groups with 15% lower plasma Ova-IgE (P = 0.04) and 35% lower Ova-IgG1 (P = 0.01) than placebo. ARA + DHA SPD resulted in 35% lower Ova-IgG1 and interleukin-6 (P = 0.04) when stimulated with lipopolysaccharide, and a higher proportion of mature B cells (OX12+, P = 0.0004 and IgG+, P = 0.008). ARA + DHA WD resulted in 20% higher Th1 cytokines (Tumor-necrosis-factor-α and interferon-γ) production to lymphocyte stimulant and higher splenocyte proportion of CD45RA+ (pan-B cells) and OX6+ (dendritic cells) than control WD (P’s < 0.05). Conclusions Combined supplementation of ARA and DHA is beneficial for the OT development, especially in the suckling period. Further, ARA + DHA supplementation can also counteract the Th2 skewed immunity of Brown Norway offspring through higher Th1 cytokines production by lymphocytes.

Effects of rosmarinic acid on immune response and intestinal microbiota in ovalbumin‐induced intestinal allergy mice

“…35 Numerous studies have reported that dietary nutrients alleviate food allergic symptoms through regulating the Th1/Th2 balance. 36,37 RA has been widely reported to relieve allergic symptoms through regulating the balance of Th1/Th2 cytokines in atopic dermatitis, allergic rhinitis, asthma and so forth. 19,38 Interestingly, the expressions of IL-4 and IL-5 were markedly upregulated in the mice of the model group, but significantly decreased by oral administration of RA (Fig.…”

“…IL‐5 is a key cytokine responsible for eosinophil activation in allergic inflammation 35 . Numerous studies have reported that dietary nutrients alleviate food allergic symptoms through regulating the Th1/Th2 balance 36,37 . RA has been widely reported to relieve allergic symptoms through regulating the balance of Th1/Th2 cytokines in atopic dermatitis, allergic rhinitis, asthma and so forth 19,38 .…”

Update on In Vitro Diagnostic Tools and Treatments for Food Allergies

“…An OVA-sensitized mouse model supplemented with olive oil had a reduction in allergic symptoms, with a reduction in cytokines associated with Th2 cells and an increase in cytokines released by Treg cells [132]. The combined supplementation with arachidonic and docosahexaenoic acids during suckling period presented beneficial effects on OVA oral tolerance of the rat offspring, revealing that this combination decreased Th2 immune response due to an increase in Th1 cytokine levels [133]. A meta-analysis study concluded that omega-3 supplementation during pregnancy reduces the risk of FA in children.…”

“…Olive oil: FA animal model [132]. Arachidonic and docosahexaenoic acids (PUFAs): mother during suckling period levels [133]. Omega-3 supplementation: mothers during pregnancy [134].…”