Statins as hypocholesterolimic drugs have recently shown to have ant-inflammatory properties and thus are being assessed for the treatment of multiple sclerosis (MS). Dietary phytosterols such as beta-sitosterol (SIT) are also hypocholesterolemic compounds and from preliminary studies they appear to have also anti-inflammatory properties. In this communication, we report on studies to investigate the immunomodulatory effects of SIT on proliferation and release of key cytokines from peripheral blood mononuclear cells (PBMC) of MS patients. In PBMC of MS patients, 16 microM SIT had no effect on cell proliferation; however simvastatin (SV) at 10 and 20 microM reduced cell proliferation by as much as 60%. SIT (4 microM) reduced TNF-alpha release by 24% in PBMC of MS patients whereas 10 microM SV reduced TNF-alpha release by 94%. 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%. In PBMC of MS patients, SIT had no effect on IL-10 release whereas 10 microM SV reduced IL-10 by 62%. SIT (4 microM) reduced IL-5 release by 47% in MS patients while 10 microM SV reduced IL-5 by 89%. 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.