Lactoferrin Reduces Allergic Symptoms and Th2-Related Cytokines in a Juvenile Murine Model of Food Allergy

Background:Food allergies, particularly to peanuts and milk, are an increasing global health concern with few safe and effective interventions. Lactoferrin (LF), a multifunctional glycoprotein abundant in human milk, has immunomodulatory and gut-protective properties. However, the therapeutic potential of LF and the mechanism of action against specific food allergies remain incompletely understood.Methods:Five-week-old female BALB/c (Bagg ALBino c series) mice were sensitized intraperitoneally with peanut protein or whey protein combined with aluminum adjuvant to establish peanut or milk allergy models. Mice were then randomized into nine groups (n = 10): normal control, allergy model, dexamethasone positive control, and low-dose (0.1 mg/kg) or high-dose (1 mg/kg) LF intervention groups. After two weeks of oral LF administration, clinical symptoms, body weight changes, serum allergen-specific Immunoglobulin G1 [IgG1] and Immunoglobulin G2a [IgG2a] levels (Enzyme-Linked Immunosorbent Assay [ELISA]), splenic T helper 2 cell [Th2] cytokines (interleukin-5 [IL-5], interleukin-13 [IL-13]), immune organ indices, and jejunal and ileal histopathology were assessed.Results:LF intervention significantly reduced clinical allergy symptoms in both peanut- and milk-sensitized mice compared with model groups. In the milk allergy model, LF significantly reduced serum levels of both IgG2a and IgG1 (≥20 pg/mL reduction; p < 0.05). The reductions were statistically significant only in the milk model (p < 0.05). LF suppressed splenic IL-5 and IL-13 secretion (≥1 pg/mL reduction; p < 0.01). LF also mitigated allergy-induced elevation of the spleen index (≥1.5% reduction; p < 0.05) and improved intestinal villus structure, with reduced inflammatory infiltration. Notably, dose- and allergen-dependent effects were observed: low-dose LF (0.1 mg/kg) was more effective for milk allergy, while high-dose LF (1 mg/kg) was more effective for peanut allergy.Conclusion:Dietary LF supplementation effectively alleviates peanut and milk allergy responses in juvenile mice, as evidenced by reduced clinical symptoms, suppression of Th2-type cytokines (IL-5, IL-13) and total IgG subclasses, and protection of intestinal barrier integrity. These findings provide preclinical evidence supporting LF as a natural nutritional intervention strategy for managing food allergies in infants and young children. However, the precise immune mechanisms remains to be further elucidated.