Whey protein hydrolysate mitigates both inflammation and endotoxin tolerance in THP‐1 human monocytic leukemia cells

INTRODUCTION: It is important to control both inflammation and immunosuppression after severe insults, such as sepsis, trauma, and surgery. Endotoxin tolerance is one of the immunosuppressive conditions and it has been known that endotoxin tolerance relates to poorer clinical outcomes in patients with severe insults. This study investigated whether whey protein hydrolysate (WPH) mitigates inflammation and endotoxin tolerance in THP‐1 human monocytic leukemia cells. METHODS: Endotoxin tolerance can be experimentally reproduced by two consecutive stimulations with lipopolysaccharide (LPS). THP‐1 cells were incubated with LPS and WPH (first stimulation). After collecting the culture supernatant to evaluate the effect on inflammation, the cells were washed and restimulated by 100 ng/ml LPS (second stimulation). The culture supernatant was again collected to evaluate the effect on endotoxin tolerance. Concentrations of LPS and WPH in the first stimulation were adjusted to evaluate their dose dependency. Cytokine levels in the supernatant were determined by enzyme‐linked immunosorbent assay. Statistical analysis was performed using the student's t‐test or Dunnett's test. RESULTS: Five mg/ml WPH significantly decreased interleukin (IL)‐6 (p = .006) and IL‐10 (p < .001) levels after the first LPS stimulation (1000 ng/ml). WPH significantly increased tumor necrosis factor‐alpha (p < .001) and IL‐10 (p = .014) levels after the second LPS stimulation. The suppressive effect of WPH on inflammation and endotoxin tolerance was dependent on the concentrations of LPS and WPH. The effective dose of WPH for endotoxin tolerance was lower than its effective dose for inflammation. CONCLUSION: WPH mitigated both inflammation and endotoxin tolerance. Therefore, WPH might be a candidate for valuable food ingredients to control both inflammation and immunosuppression after severe insults.