Is there a link between cholesterol and IL-6 levels in human? An in vivo and in vitro study

Previous studies suggested that interleukin-6 (IL-6) affects the reduction of serum lipoprotein LDL cholesterol levels during acute inflammation. We have investigated the association between cytokines and cholesterol levels in normal subjects and moderate hypercholesterolemic patients. Moreover, cultured human microvascular endothelial cells (HMEC-1) were treated with low density lipoproteins (LDL-C) to verify whether IL-6 expression is modulate during the treatment. Blood samples of all subjects were assayed for serum lipid, TNFα and IL-6 levels. HMEC-1 cells were treated for 24 h with increasing concentrations of LDL-C in presence and absence of the TXA2 receptor antagonist SQ29.548. Normal subjects and patients with moderate hypercholesterolemia showed significant difference in IL-6 serum levels (P < 0.01), in contrast the levels of TNFα resulted unaffected. The entire population analyzed showed a high significant inverse correlation between LDL-C and serum IL-6 concentrations (P < 0.001). In the in vitro study a significant increasing of IL-6 medium concentrations were obtained at the higher two LDL-C doses (P < 0.05, P < 0.01), whereas in presence of SQ29.548 such effect was inhibited. These data provide further confirmation on the regulatory role of IL-6 in humans; in addition they seem to suggest the presence of a positive feed-back in the in vitro microvascular cell system, in relation to increasing concentrations of LDL-C. The cause of this effect seems to be related to the production of 8-isoprostane, a metabolite of lipid peroxidation.