The effect of phytosterols on the cytokine release from monocytes from multiple sclerosis patients

Objectives. To assess the immunomodulatory effects of the plant sterol, beta-sitosterol, on peripheral blood mononuclear cells of multiple sclerosis (MS) patients and to compare its effects to those of simvastatin.;Background. MS is a degenerative chronic disease of the central nervous system (CNS). The disease is characterized by the presence of plaques in white and grey matter of the CNS. Demyelination of axons, activation of microglial, and infiltration of immune cells are also key features of acute MS lesions. Studies have shown that macrophages play a critical role in the development of MS. Macrophages produce pro-inflammatory cytokines such as TNF-alpha and anti-inflammatory cytokines such as IL-10. Recent studies have shown that cholesterol lowering drugs, such as statins, may have anti-inflammatory properties and thus have a place in MS treatment. Work from our and other labs suggests that plant sterols (phytosterols) may also have similar properties to statins and thus may be used also in the treatment of MS patients.;Methods. Peripheral blood mononuclear cells (PBMC) from 11 untreated MS patients and 7 controls were treated with 0, 4, 16 and 32 microM of beta-sitosterol (SIT) or 0, 1, 10 and 20 microM of simvastatin (SV). Cell proliferation and secretion of cytokines, TNF-alpha, IL-12, IL-10 and IL-5, after phytohemagglutinin (PHA) treatment were measured.;Results. SIT (4 microM) reduced TNF-a release by 24% in PBMC of MS patients whereas simvastatin (SV) reduced TNF-alpha release by 94% at 10 microM. SIT reduced IL-12 release in MS patients at 4 and 16 microM by 27% and 30%, respectively. In healthy subjects, 16 microM SIT increased the anti-inflammatory cytokine IL-10 by 47% whereas 10 microM SV decreased IL-10 by 30%. SIT had no effect on IL-10 release from PBMC of MS patients whereas 10microM SV reduced IL-10 by 62%. SIT (4microM) reduced IL-5 release by 47% in MS patients while 10 microM SV reduced IL-5 by 89%.;Conclusions. The results show that SIT is effective in modulating the secretion of pro/anti-inflammatory cytokines and suggest a potential beneficial effect of SIT in MS management without the side effects associated with statin therapy.