Natural products inhibit LPS-induced activation of pro-inflammatory cytokines in peripheral blood mononuclear cells.

Haemodialysis (HD) patients have many biochemical, immune and inflammatory alterations that can lead to an increased risk for cardiovascular disease. The two major factors affecting these disorders are (a) metabolic, biochemical, immune or inflammatory alterations due to the uremic syndrome per se and (b) alterations due to the therapeutic treatments of uremia, especially HD-induced stress. HD-induced stress includes activation of the pro-inflammatory transcription factor NF-kappaB. In the present study, we have employed lipopolysaccharide (LPS) to activate the peripheral blood mononuclear cells (PBMC), as a model of HD-induced stress. The natural products curcumin, resveratrol and parthenolide are known inhibitors of the activation of NF-kappaB. PBMCs were treated with various concentrations of curcumin, resveratrol and parthenolide and tested for the abilities of these natural products to protect against the LPS-induced expression, secretion of the pro-inflammatory cytokines TNFalpha, IL-1beta and IL-6 and activation of the pro-inflammatory COX-2. We report here that parthenolide is an especially effective natural product that limits the development of a pro-inflammatory state by preventing the activation of all four of these pro-inflammatory signals. The approach of limiting the development of a pro-inflammatory state in HD patients during the dialysis procedure by addition of a natural product that protects against activation of NF-kappaB might be a clinically useful approach to protect leukocytes from HD-induced stress.