Abstract Details

Title Effects of Smoke Exposure on the Course of Multiple Sclerosis II. Role of the Renin-Angiotensin System

Topic MS and Related Diseases

Presentation(s) P04 - (-)

Poster/Presentation
Number 134

Objective

Background BACKGROUND: We and others have previously demonstrated that smoking is associated with worse disease course. The RAS is a major regulator of blood pressure. However, recent evidence has demonstrated that RAS also plays a major role in autoimmunity. In addition, studies showed serum angiotensin I converting enzyme (ACE) activity increased significantly after smoking.

Design/Methods DESIGN/METHODS: Sixty patients with clinically isolated syndrome (CIS), and 40 healthy controls were studied. Production of renin, ACE, CCL-2, CCL-3, CCL-5, and CXCL10 were measured by ELISA. Expression of angiotensin type 1 receptor (AT1R) on monocytes and T cells was assessed by RT-PCR. Production of IL-6, IL-10, IL-13, IL-17, IL-22, IFN-?, TGF-?, and anti-MOG antibodies were assessed by ELISPOT. CD4+CD25+Foxp3+ regulatory T cells (Treg) were measured by flow cytometry.

Results RESULTS: Smoker CIS patients demonstrated higher risk of developing clinically definitive MS, and a shorter time to first relapse compared to non-smokers. Both renin and ACE, production were increased in culture supernatants of autoreactive T cells and monocytes from smoker patients. Likewise, AT1R mRNA expression was significantly higher in both T cells and monocytes from patients who smoked compared to non-smokers and normal controls. Smoker patients showed increased production of IL-6, IL-13, IL-17, IL-22, anti-MOG antibodies, CCL2, CCL3, and CXCL10, as well as decrease in the number of Treg cells. Inhibition of ACE using enalapril, and blocking of AT1R using losartan suppressed increased production of IL-17, IL-22, CCL2, CCL3 and CXCL10 and promoted the expansion of Treg cells.

Conclusions CONCLUSIONS: Smoker MS patients demonstrated increased activity of the RAS. This pathway could be one the factors explaining more severe course of MS in smoker patients.

Authors/Disclosures
Jorge D. Correale, MD (Institute for Neurological Research) PRESENTER	Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Correale has received research support from Merck. The institution of Dr. Correale has received research support from Biogen. The institution of Dr. Correale has received research support from Novartis .
Mauricio F. Farez, MD (FLENI)	Dr. Farez has received personal compensation for serving as an employee of Entelai. Dr. Farez has stock in Entelai. The institution of Dr. Farez has received research support from Fundación Sadosky.
	No disclosure on file

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