**5. Whey proteins leads to activation and production of pro-inflammatory cytokines**

As cellular antioxidants struggle to keep up with ROS, the organism suffers from oxidative stress [67]. Inflammation causes damage to tissue by releasing free radicals from macrophages and neutrophils [68]. By transporting iron, whey proteins are essential for maintaining oxidative stress [69]. They produce the cytotoxic protection mechanism of neutrophils as well as free radicals [70, 71]. Whey proteins are involved in the preservation of inflammation through reducing lipid peroxidation and oxygen radicals via the production of antioxidant glutathione. Inflammatory cytokines are generated in large part by whey proteins. Whey proteins supplementation restored a high degree of IL-1β and TNF-α. IL-1β and TNF-α influenced the expression of chemokines and the adhesion of molecules required for the recruitment of inflammatory cells [72, 73]. According to a review, whey protein can increase neutrophil infiltration by inhibiting oxidative markers and reactive oxygen species. In whey protein treated mice, the number of bone marrow-derived dendritic cells, T-cells, and B-cells increased in response to CCL-21 and CXCL-12 [74]. Cytokines released by neutrophils increase the proliferative and remodeling processes of cells; via this, the earliest signals responsible for the activation of fibroblasts and keratinocytes are produced [75, 76]. Neutrophils are involved in the early stages of the anti-inflammatory cascade by removing bacteria and phagocytosing cellular waste [77]. Various experiments have shown that priming blood neutrophils with proteins can trigger oxidative explosion, chemotaxis, degranulation, and phagocytosis [78]. Whey protein promotes the development of inflammatory proteins such as IL-1β, IL-8, IL-6 and TNF-α in macrophages [78, 79]. The initiation of NF-kB, which contributes to the development of inflammatory cascades and the release of pro-inflammatory cytokines for instance IL-1β, TNF-α, and IL-6 is one of whey protein's anti-inflammatory processes [80, 81]. Inflammatory cytokines such as IL-1, IL-1, IL-10, and TNF-α were shown to be lower in the blood of mice feeding whey protein concentrate. Contrary to this, the amounts of cytokines such as IL-2, IL-4, IL-7, and IL-8, which are accountable for maintaining a healthy immune system, increased. The proliferative capacity of lymphocytes, monocytes, and macrophages in reaction to antigens was intensified [82].
