Abstract Details

Title The role of IL-11+ monocytes in relapsing-remitting multiple sclerosis (RRMS) and experimental autoimmune encephalomyelitis (EAE)

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 121

Objective

To study the role of IL-11-secreting monocytes in the pathogenesis of RRMS.

Background

We have previously shown that IL-11 is highly upregulated in the CSF of untreated patients with clinically isolated syndrome (CIS), suggestive of its role in the inflammatory response in MS. In this study, we examined the role of monocytes in the IL-11-induced inflammatory response in RR MS.

Design/Methods CD14⁺ monocytes from 23 untreated RRMS patients and 14 age-, sex- and race-matched HCs were examined by flow cytometry. Anti-IL11 mAb was used in RREAE to determine its therapeutic potential.

Results The frequency of IL-11-secreting CD14⁺ cells was significantly increased in PBMCs from 14 RRMS patients in comparison to matched HCs (p=0.04). In RRMS patients, CD14⁺IL-11⁺ cells are enriched in the CSF as compared to the paired blood samples (p=0.02). In RRMS patients the co-expression of pro-inflammatory IL-23 was significantly higher than the expression of anti-inflammatory cytokine IL-10 in IL-11⁺CD14⁺ cells. IL-23⁺IL-11⁺CD14⁺ cells from RRMS patients had a higher CCR2 expression in comparison to HC (p=0.03), suggestive of their potential to migrate to the CNS. In-vitro studies with purified CD14⁺ cells from RRMS patients showed that IL-11 increases the expression of IL-23 (p=0.01). RREAE experiments showed that anti-IL-11 mAb treatment at the onset of disease (5 mg/kg, i.p, daily for 10 days) decreased the clinical scores in comparison to the isotype control group (n=12/group, p<0.05). Anti-IL-11 mAb treatment decreased the frequency of IL-23⁺ monocytes and increased the frequency of regulatory IL-10⁺ monocytes in the CNS and PBMCs at 21 days p.i. (n=6/group, p=0.06, 0.01). Treated mice also had decreased IL-11⁺, IL-17A⁺, GM-CSF⁺ and IFNg⁺CD4⁺within the CNS.

Conclusions IL-11-secreting monocytes contribute to the inflammatory response in early RRMS. Anti-IL-11 mAb treatment of RREAE ameliorated the clinical disease, in part by inducing regulatory monocyte expansion.

Authors/Disclosures
Maryamsadat Seyedsadr, PhD (Thomas Jefferson Hospital) PRESENTER	Maryamsadat Seyedsadr has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Jocelyn H. McGuire, NP (Norton Neuroscience Institute)	Mrs. McGuire has nothing to disclose.
Dhanashri P. Miskin, MD (Thomas Jefferson University)	Dr. Miskin has nothing to disclose.
Silva Markovic-Plese, MD, FAAN (Thomas Jefferson University)	Dr. Markovic-Plese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Markovic-Plese has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.

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