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Abstract Number: 345

A Low Salt Diet Ameliorates Clinical Manifestations in Collagen-Induced Arthritis

Bettina Sehnert1, Sandy Pohle2, Agnes Schröder3, Jens Titze3,4 and Reinhard E. Voll5, 1Rheumatology and Clinical Immunology & Centre of Chronic Immunodeficiency,, University Hospital Freiburg, Freiburg, Germany, 2Department of Internal Medicine 3, University of Erlangen-Nürnberg, Erlangen, Germany, 3Interdisciplinary Center of Clinical Research, Research Group N2, Nikolaus Fiebiger Center of Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany, 4Department of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 5Rheumatology and Clinical Immunology & Centre of Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Mouse model

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Session Information

Session Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose

A genetic predisposition, but also environmental factors including infections and smoking modulate manifestation and severity of inflammatory autoimmune disease like rheumatoid arthritis (RA). Recently, the induction of pathogenic Th17 cells as a consequence of  increased salt intake was demonstrated in an animal model of multiple sclerosis.  The impact of dietary factors such as low salt consumption on the inflammatory status in arthritis has not yet fully characterized. The aim of the study was to investigate the association between salt intake and clinical manifestations in a mouse model of arthritis.

Methods

DBA/1 mice were immunized with bovine type II collagen (CII) in complete Freund’s adjuvant (CFA). Two weeks before immunization experimental diet was started and the mice were divided in two groups. The LS (low-salt) group (n=9) received a diet containing a sodium content  <0.03% and tap water.  The HS (high-salt) group (n=10) were fed with a diet containing 4 % NaCl  in combination with 0.9% NaCl supplemented tap water. The feeding lasted 62 days.  Arthritis severity was assessed by clinical scoring to a graded scale (0-4). At the end of the experiment hind paws were removed for histological analysis. The stained sections (hematoxylin/eosin, toluidine blue and tartrate-resistant acid phosphatase) were graded on a scale from 0-3. Levels of IgG1 and IgG2a antibodies against bovine collagen type were measured by ELISA.

Results

Administration of a low salt diet resulted in a decreased arthritis severity compared to the HS-group. Further, the incidence of arthritis was significantly lower in the LS group.  The histopathological analysis revealed reduced infiltrations with inflammatory cells in the group fed with the low salt diet.  Also the destruction of cartilage and bone was less pronounced in the LS compared to the HS group. ELISA experiments showed that the level of pathogenic IgG2a antibodies against CII was markedly increased in HS-mice, whereas low salt consumption reduced anti-CII IgG2a levels significantly. The titers of CII-specific IgG1 were similar in both groups.  This resulted in decreased IgG2a:IgG1 ratio in the LS group and indicates a shift toward a more Th2-dominated immune response.

Conclusion

Low salt diet ameliorates clinical and histological signs in murine collagen-induced arthritis. The low salt consumption inhibits the humoral IgG2a response against CII and protects against antibody-mediated joint destruction. We conclude that a low salt diet might ameliorate RA and support treatment of immune-mediated arthritides.


Disclosure:

B. Sehnert,
None;

S. Pohle,
None;

A. Schröder,
None;

J. Titze,
None;

R. E. Voll,

Investigator,

5.

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