Abstract:The immunomodulatory effect of whey protein combined with casein phosphopeptide on immunosuppressed mice was studied.Cyclophosphamide-induced mouse model of immunosuppression was established，and the model mice were randomly assigned into a model group，a whey protein group，and a whey protein combined with casein phosphopeptide group.The healthy mice were selected as the control group.The protection mechanism was explored based on histopathological observation，oxidative stress index，inflammatory signaling pathway，and cytokine expression.The results showed that whey protein combined with casein phosphopeptide alleviated the slow weight gain，increased the glutathione content and superoxide dismutase activity in spleen and small intestine，and mitigated the histopathological injury of spleen and small intestine in immunosuppressed mice.Furthermore，it inhibited the activation of TLR4/MyD88/NF-κB inflammatory signaling pathway and the production of inflammatory cytokines in spleen.In summary，the combination of whey protein and casein phosphopepin could increase the activity of antioxidant enzymes，protect the immune system from oxidative damage，and inhibit the inflammatory response of immunosuppressed mice，which may involve the regulation of TLR4/MyD88/NF-κB inflammatory signaling pathway.