FOXP3 and cytokine profile in patients with optic neuritis

Background: Acute mono-symptomatic optic neuritis (ON) is a common first manifestation of multiple sclerosis (MS). The pathogenesis of ON involves a myelin antigen T-cell mediated autoimmune response (as in MS) which leads in the demyelination of the optic nerve. The immunological response is closely controlled by cytokines and T-regulatory cells. A disturbance in the net balance between pro-inflammatory and anti-inflammatory cytokines may play an important role for the progression from mono-symptomatic ON to clinically definite MS. Recent studies suggest that the expression of FOXP3 is mainly by T-reg cells and that the expression of FOXP3 is reduced in patients with relapsing-remitting MS (RRMS). Objective: The aim of the study was to investigate the FOXP3 mRNA expression profile along with the transcript expression level of both pro and anti-inflammatory cytokines in patients with ON compared with a sex and age-matched healthy control (HC) group. Methods: In this study we examine 1) a group of untreated patients with acute ON, 2) a group of HC matched in age and gender, for the expression of FOXP3, pro-inflammatory (IFN- gamma , TNF- alpha , IL-12), immune suppressive (IL-10, IL-4, TGF- beta ) and other cytokines (IL-2, IL-5, IL-6) with real time PCR. T-student parametric test was used to evaluate the statistical significance. Results: IFN- gamma (1.30 fold; P=0.0162), TGF- beta (0.48 fold; P=0.01) and IL-4 (2.30 fold; P=0.0472) were statistically significantly elevated in ON. No significant alteration between the groups was observed regarding the expression levels of FOXP3 mRNA and the above mentioned cytokines. Conclusions: The elevation of IFN- gamma , TGF- beta and IL-4 transcription supports the theory that ON is an inflammatory condition where pro- and anti-inflammatory mechanisms are involved in the down-regulation of the disease. FOXP3 gene expression in ON is not different from the HC, which may suggest that already in the early stages of demyelinating disease, patients are not able to mobilize FOXP3 and are therefore unable to down-regulate the inflammation.