Yonsei Med J.  2019 Jan;60(1):88-97. 10.3349/ymj.2019.60.1.88.

Sodium Chloride Aggravates Arthritis via Th17 Polarization

Affiliations
  • 1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 2Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. juji@catholic.ac.kr

Abstract

PURPOSE
Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans.
MATERIALS AND METHODS
Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients.
RESULTS
NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid.
CONCLUSION
This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.

Keyword

Rheumatoid arthritis; salt; sodium chloride; Th17 cells; collagen-induced arthritis

MeSH Terms

Animals
Arthritis*
Arthritis, Experimental
Arthritis, Rheumatoid
Autoimmune Diseases
Diet
Flow Cytometry
Humans
Interleukin-17
Intestines
Joints
Mice
Monocytes
Osteoarthritis
Sodium Chloride*
Sodium*
Spleen
Synovial Fluid
T-Lymphocytes, Helper-Inducer
Th17 Cells
Interleukin-17
Sodium
Sodium Chloride
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