High protein diet increases the risk of allergic sensitization but not asthma in mice through modulation of the cytokine milieu toward Th2 bias.

Introduction: The role of different nutrients in allergic sensitization is not clear. In this study we aimed to determine the effect of high protein (HP) diet on allergic sensitization, cytokine profile, and asthma in mice. Methods: Seven- to eight-week old female BALB/c mice were fed either normal (ND) or HP diet and were sensitized with ovalbumin intraperitoneally followed by intranasal challenge. Allergic sensitization was tested by measuring anti-ovalbumin (OVA) IgE, IgG1, and IgG2a antibodies. Cytokine levels were tested by multiplex ELISA in splenocyte supernatants after stimulation. Airway inflammation was tested by measuring total and differential cell counts in bronchoalveolar lavage fluid and by measuring bronchial mucus production, goblet cell hyperplasia and perivascular and peribronchial inflammation severity scores by histologic examination. Results: Mice fed HP diet had a significant increase in weight and higher levels of OVA-specific IgE and IgG1 antibodies compared to the ND group (P-values 0.002, 0.007 and <0.001, respectively). In addition, they showed a selective Th2 bias in cultured splenocyte supernatants compared to the ND group as demonstrated by higher IL-4 and IL-6 levels (P-values <0.001 and 0.011, respectively) and higher ratios of Th2 to Th1 cytokines. However, the level of airway inflammation was comparable between both groups. Conclusions: HP diet increases the risk of allergic sensitization though increase in Th2 cytokines. Efforts should be made to define the upper limit of protein in the diet that does not predispose to allergic sensitization. The effect of diet on health should remain a focus of research for the establishment of optimal health and resilience.