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

Exp Mol Med. 2012 Jul 31;44(7):424-31. doi: 10.3858/emm.2012.44.7.047.

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-α. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Adipokines
  • Collagen Type II
  • Interleukin-17
  • Interleukin-6
  • Tumor Necrosis Factor-alpha