Innate immunomodulatory effects of cereal grains through induction of IL-10

Background: Interactions between the gastrointestinal immune system and the luminal environment play critical roles in maintaining immune homeostasis and in diseases such as inflammatory bowel disease. Although immunomodulation by microbial factors has been studied extensively, little attention has been given to the potential immunomodulatory effects of ingested foods. Objective: We characterized the effects of cereal grains on the immune response in human subjects and investigated the mechanism. Methods: PBMCs from healthy individuals were incubated with cereal grain extracts, and cytokine levels in cell-free supernatants were measured. The cellular source of IL-10 and the role of monocytes were investigated by means of flow cytometry and cell-depletion/reconstitution experiments. Results: Extracts of cereal grains, including rice and wheat, induced marked IL-10 production from PBMCs. Intracellular cytokine staining and cell-depletion experiments showed that CD14⁺ monocytes produced IL-10. Importantly, when PBMCs were stimulated with concanavalin A, cereal grains concentration-dependently inhibited their production of IL-5, IL-13, and IFN-γ; neutralizing IL-10 or removing the monocytes abrogated this inhibitory effect. This cereal grain-induced IL-10 response was polymyxin B sensitive, heat resistant, and inhibited by blocking the Toll-like receptor 4. Conclusion: Cereal grains have strong innate immunomodulatory effects by inducing marked production of IL-10 from CD14⁺ monocytes in vitro. LPS or LPS-mimicking activity in cereal grains might be responsible. The potential immunomodulatory effects of cereal grains need further study in vivo.