Exp Mol Med.  2012 Jul;44(7):424-431.

Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation

• Jhun JY
• Yoon BY
• Park MK
• Oh HJ
• Byun JK
• Lee SY
• Min JK
• Park SH
• Kim HY
• Cho ML

Abstract

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-alpha. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.

Keyword

arthritis, experimental; inflammation; mice; obesity; Th17 cells

MeSH Terms

Adipokines/immunology/metabolism
Animals
*Arthritis, Experimental/genetics/immunology/pathology
Cell Differentiation/genetics/immunology
*Collagen Type II/administration & dosage/immunology
Disease Models, Animal
Gene Expression
Humans
Inflammation/chemically induced/*immunology
Interleukin-17/metabolism
Interleukin-6/blood
Joints/immunology/pathology
Mice
Mice, Inbred C57BL
*Obesity/genetics/immunology/pathology
*Th17 Cells/immunology/metabolism
Tumor Necrosis Factor-alpha/blood