Background There is a complex relationship between nutrition and the immune system, which is only partially understood. Especially, the impact of nutrition on inflammatory autoimmune diseases like rheumatoid arthritis (RA) requires further investigations. It was recently shown that an increased salt intake aggravates the clinical symptoms in an animal model of multiple sclerosis by inducing pathogenic Th17 cells . However the effect of dietary factors such as low salt consumption on the inflammatory status in arthritis is poorly investigated.
Objectives In this study we examined the effect of low salt diet in a mouse model of arthritis and identified its underlying mechanisms.
Methods Two weeks before immunization with bovine type II collagen (bCII) in complete Freund's adjuvant (CFA) the experimental diet was started in DBA/1 mice. The low salt group (n=9) received a diet containing a sodium content <0.03% and tap water for 62 days, whereas the high-salt group (n=10) was fed with a diet containing 4% NaCl and 0.9% saline solution. Arthritis severity was assessed by clinical scoring using a graded scale (0-4). Hind paws were prepared for histological analysis. Levels of anti-CII autoantibodies were measured by ELISA. Homogenates from hind paws were prepared and cytokines were assessed by ELISA. mRNA levels of inflammatory cytokines in the spleen were determined by qRT-PCR.
Results In CIA the low salt diet decreased severity and incidence of arthritis compared to the high salt group. The histology showed reduced infiltrations with inflammatory cells after low salt diet. Also cartilage breakdown and bone destruction was less pronounced in the low salt compared to the high salt group. ELISA experiments showed that the level of pathogenic IgG2a antibodies against CII was markedly elevated in high salt mice, whereas low salt consumption reduced anti-CII IgG2a levels significantly. CII-specific IgG1 titers were increased in the low salt versus the high salt group. This resulted in decreased IgG2a:IgG1 ratio in the low salt group and indicates a shift toward a more Th2-dominated immune response. Already 20 days after immunization we observed decreased levels of MCP-1 and IL-1β and an increase in IL-10 in paw extracts of mice which had received a low salt diet. Further, in low salt mice mRNA levels of IFNγ, IL-6 and IL-1β were reduced.
Conclusions Lowering the salt intake attenuates clinical and histopathological manifestations in collagen-induced arthritis. The low salt diet protects against antibody-mediated joint destruction through a Th2 shift and a decreased expression of potential mediators of inflammation. We conclude that a low salt diet could be a useful supplementary nutritional therapy of immune-mediated arthritides.
Kleinewietfeld, M., et al., Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature, 2013. 496(7446): p. 518-22.
Disclosure of Interest None declared
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