A chronic low-grade inflammatory state accompanies obesity, evident from both elevated systemic inflammatory markers in serum and infiltration of inflammatory cells into tissues. In obese humans, serum levels of pro-inflammatory cytokines are elevated and peripheral blood mononuclear cells are activated [
82]. Inflammatory cytokines can increase insulin resistance and inhibit glucose uptake in peripheral tissues, as well as increase proteolysis of skeletal muscle cells. Evidence from
in-vitro studies suggests that dairy proteins and milk derived peptides have immunosuppressive or immunostimulatory effects [
29]. Kappa-casein has been reported to suppress lymphocyte proliferation induced by T and B cell mitogens [
83]. Whey protein and its hydrolysates have been to inhibit the proliferation of lymphocytes, without the induction of apoptosis [
84]. When mitogens or antigens activate T lymphocytes they produce cytokines and upregulate cell surface immune receptors. Whey proteins lactoferrin and lactoperoxidase have been shown to suppress interferon secretion from mitogen activated lymphocytes [
85]. Animal studies indicate whey protein and casein or their peptides have immunomodulatory effects
in-vivo, but these are not always in concordance with effects observed
in-vitro[
29]. There have been very few studies on whether whey protein or casein can modulate inflammation and immune response in individuals with impaired metabolic control. A recent study in obese non-diabetic individuals given a high fat mixed meal and whey protein isolate revealed the CCL5 response, an indicator of immune activation, in the 4 h postprandial period [
86]. In addition, the MCP-1 response was higher after the whey protein isolate compared to other proteins [
86]. Another recent study in patients undergoing surgery reported that a whey protein and CHO drink decreased the postoperative acute phase response and insulin resistance [
87]. Conversely, in a group of overweight postmenopausal women, a 45 g whey protein isolate or sodium caseinate bolus did not decrease postprandial plasma inflammatory markers, IL-6, TNF-α or acute phase C-reactive protein (CRP) over a 6 hour period compared to glucose ingestion [
81]. Similarly, in a longer term study in overweight and obese individuals, whey protein or casein supplementation for 12 weeks was reported not to influence plasma inflammatory markers [
77]. However, in patients with chronic obstructive disease (COPD) undergoing a low-intensity exercise therapy, whey peptide was found to decrease circulating IL-6, IL-8, TNFα and hsCRP, accompanied by an increased exercise tolerance [
88]. While
in-vitro evidence indicates that whey protein and casein have immunomodulatory effects, more
in-vivo studies are required to assess whether these proteins can modulate the immune response in individuals with impaired metabolic health and low-grade inflammation.