Previous reports including our own have shown low levels of vitamins E and A(Reference Ghebremeskel, Williams and Harbige1, Reference Jimenez-Jimenez2) increased or decreased Zn and Cu(Reference Palm and Hallmans3–Reference Kapaki5) and elevated pro-inflammatory cytokines(Reference Beck6–Reference Hollifield, Harbige and Pham-Dinh8) in the blood and CSF of multiple sclerosis (MS) patients. The aim of this study was to investigate the relationships between the levels of circulating plasma vitamins E and A, Zn, Cu, interferon-γ (IFNγ), TNFα and IL-6 in MS patients in the remission phase of the disease compared with healthy controls. IFNγ, TNFα and IL-6 were assayed using commercially available paired antibodies (Genzyme Diagnostics Inc., UK) in an ELISA format. Vitamins A and E were extracted in ethanol and determined using HPLC (Philips PU 4100) equipped with a PU 4110 UV/visible detector and C18 reverse phase column. Determination of Cu and Zn was by ICP-MS (Perkin Elmer 5000 ICP-MS). There was no significant difference in the mean plasma levels of vitamin A, Zn, Cu, IFNγ, TNFα and IL-6 between MS patients and healthy controls (Table). There was, however, a significantly (P<0.001) lower plasma vitamin E concentration in patients with MS compared with controls and the mean concentrations of IFNγ, TNFα, IL-6 and copper were elevated compared with healthy controls (Table).
MS, multiple sclerosis patients n 21 aged 22–68 years with relapse-remitting disease (expanded disability status score 2–4.5) TNF-α (n 16), IL-6 (n 8); HC, healthy controls (n 9) aged 25–45, IL-6 (n 4). *P<0.001.
Plasma vitamins A and E were positively correlated (P<0.03, r=0.46) in MS patients and in healthy controls (P<0.04, r=0.6). In MS patients only, a positive correlation between plasma IFNγ and TNFα (P<0.0001, r=0.91) and also between Zn and vitamin A (P<0.07, r=0.4) was observed as well as a negative correlation between Zn and IL-6 (P<0.07, r=0.64). These findings suggest that pro-inflammatory cytokines such as IL-6 may be responsible, in part, for some of the previously observed alterations in circulating nutrients in patients with MS, i.e. Zn and vitamin A. The low plasma vitamin E finding in MS compared with controls is consistent with our earlier observations in MS(Reference Ghebremeskel, Williams and Harbige1) although the present values were higher both in controls (1.7-fold) and MS (1.8-fold) than we previously reported which may indicate an increase in the intake of vitamin E in the general and MS population since the original study. Moreover, vitamin E is an important membrane lipid antioxidant and given the importance of PUFA in MS(Reference Harbige and Sharief9) it should be further investigated in patients with MS both in remission and relapse phases of the disease and in relation to membrane PUFA.