Hyperlipoproteinemia affects cytokine production in whole blood samples exvivo. The influence of lipid-lowering therapy

Low-density lipoprotein (LDL)-receptor deficient mice, thus hypercholestero lemic, combine protection against infection with an ex vivo two- to threefo ld higher pro-inflammatory cytokine production in macrophages. A pro-inflam matory cytokine profile ex-vivo is also associated with survival of gram-ne gative sepsis in man. We hypothesized that high lipoprotein levels would be associated with a pro-inflammatory cytokine production and could explain t he resistance to fatal infection. We treated 10 patients with familial hype rcholesterolemia (FH) with HMG-CoA reductase inhibitors, and 13 patients wi th endogenous hypertriglyceridemia (HTG) with fibrates. Blood samples were stimulated ex vivo with lipopolysaccharide (LPS), to assess the cytokine pr oduction capacity. FH patients had significantly lower tumor necrosis facto r-alpha (TNF-alpha) production, compared to normolipidemic controls (P = 0. 001). Lipid lowering treatment in FH patients did not affect TNF-alpha prod uction. HTG patients showed significantly higher TNF-alpha production at ba seline than matched normolipidemic controls (P < 0.001), while lowering of serum triglycerides in these patients resulted in a significant decrease in TNF-alpha production (P = 0.019). The IL-10 production was not affected. T hese data refute our hypothesis that high LDL-cholesterol levels are associ ated with a pro-inflammatory cytokine production capacity. In contrast, the study suggests that very-low-density lipoprotein (VLDL) in hypertriglyceri demic patients augments TNF-alpha production. (C) 2000 Elsevier Science Ire land Ltd. All rights reserved.