Plant Sterols Increased IL-6 and TNF-alpha Secretion from Macrophages, but to a Lesser Extent than Cholesterol

Aim: Phytosterolemia is an inherited disorder characterized by hypercholesterolemia and premature atherosclerosis, together with increased inflammatory states in some cases. The underlying mechanisms of atherogenesis in phytosterolemia, however, have not been completely elucidated. In this study, we investigated whether phytosterols would affect inflammatory reactions in macrophages and macrophage cell lines. Methods: We incubated RAW264.7 cells (RAW) and mouse peritoneal macrophages (MPMs) with sitosterol (Sito), campesterol (Camp) or cholesterol (Chol) at low (8 mu M, 16 mu M) or high (160 mu M) concentrations, and investigated their effects on LPS-induced secretion of IL-6 and TNF-alpha. We also analyzed their effects on endoplasmic reticulum (ER) stress in both cells, and on the cell proliferation of RAW. Results: At low sterol concentrations, only Chol resulted in a tendency toward the increased secretion of TNF-a from MPMs. At high concentrations, Chol induced a significant increase in TNF-alpha secretions from both cells; however, Sito resulted in a non-significant increase in TNF-alpha secretion. The effects on IL-6 secretions of Sito were also significantly less than those of Chol. Camp increased the secretions of both cytokines from MPMs; however, the extent of these increases was less pronounced than that of Chol. Augmentation of ER stress was greatest with Chol among the sterols, and the proliferation of RAW cells was inhibited only with Chol. Conclusion: The lesser degree of inflammatory reactions and toxicity in macrophages with phytosterols than with cholesterol suggests that plant sterols themselves might not be primarily responsible for atherogenesis in phytosterolemia.