Cytokine profile, Foxp3 and nuclear factor-kB ligand levels in multiple sclerosis subtypes

Patients with multiple sclerosis (MS) present with heterogeneous clinical courses. To elucidate whether different immunopathological mechanisms are involved in MS subgroups, we compared serum levels of TNF-α, IL-1β, hs-CRP, receptor activator of nuclear factor kappa-B ligand (RANKL) and peripheral blood foxp3 expression in clinical subtypes of MS (relapsing remitting: RR-MS; secondary progressive: SP-MS; primary progressive: PP-MS) and healthy subjects.

In a case-control study, 72 healthy individuals and 72 age- and sex-matched multiple sclerotic patients (57% RR-MS, 18% SP- MS and 25% PP-MS) were evaluated. The age, gender distribution, and BMI of MS patients in these three sup-types were similar. The serum levels of TNF-α, IL-1β, and RANKL were measured by ELISA. hs-CRP was measured by imunoturbidimetric method. Peripheral blood mononuclear cells expression of Foxp3 was measured by real time PCR.

A significant elevation of TNF-α, hs-CRP, IL-1β and RANKL and diminution of Foxp3 expression in MS patients compared to control was found (P<0.001). PP-MS had highest levels of TNF-α, IL-1β, CRP and RANKL, and lowest levels of foxp3, with difference in TNF-α reached significant level (P<0.01). RANKL and TNF-α showed a reverse (P<0.01) significant correlation with Foxp3 relative expression levels. Patients with early age onset (onset before 30 years) had significantly higher levels of hs-CRP compared to late age onset patients.

These data demonstrate the presence of immunopathogenesis differences between relapsing and non-relapsing form and is also the first to stress a role for cytokine RANKL in MS patients.