Increased IL-27 Cytokine Levels in the Cerebrospinal Fluid but Not in the Blood of Multiple Sclerosis Patients (P02.083)

Abstract

Objective: To measure Interleukin (IL)-27 levels in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients compared to healthy controls (HC) or patients suffering from non inflammatory neurological diseases (NIND). Background IL-27, an heterodimeric cytokine with both pro- and anti-inflammatory properties, is involved in autoimmune diseases pathogenesis. IL-27 can be produced directly at the inflammation sites by local resident cells and Antigen Presenting Cells (APC). In vitro, IL-27 can be secreted by resident cells of the central nervous system such as astrocytes or microglia. However, it is not known whether IL-27 levels are modified in blood or CSF of MS patients. Design/Methods: We performed a cases study analysis. Protein levels of IL-27 were measured by ELISA from A) the blood of HC (n=23), patients with relapsing remitting (RR)MS without treatment (n=30) or treated with Interferon beta (n=28), Glatiramer acetate (n=24) or Natalizumab (n=12), B) the CSF of untreated patients with RRMS (n=56), optic neuritis (ON) (n=29) or NIND (n=42). Differences in variables were analyzed using Student t tests (for normally distributed data) or MannWhitney U tests (for non-normally distributed data). Results: IL-27 levels were significantly elevated in the CSF of patients with RRMS but not with isolated ON compared with patient with NIND. By contrast, IL-27 plasma levels of RRMS patients were equivalent to HC and were not influenced by immunomodulatory drugs. Conclusions: Our results show increased levels of IL-27 cytokine in the CSF but not in the blood of MS patients compared to controls. Those results highlight the importance of IL-27 during autoimmune disease in human. IL-27 has anti-inflammatory properties and local production of IL-27 in the brain could sign the induction of a regulatory response. The effect of new immunodulatory therapies on cerebral IL-27 production should be investigated and could help understand the biology of IL-27 in MS. Supported by: Swiss National Foundation, Novartis Foundation, FP7 Marie Curie. Disclosure: Dr. Pot Kreis has nothing to disclose. Dr. Juillard-Mochon has nothing to disclose. Dr. LaLive has nothing to disclose.