Interleukin 6 plays a key role in the development of antigen-induced arthritis.

Abstract

To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight generations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.

• Authors: S Ohshima, Y Saeki, T Mima, M Sasai, K Nishioka, S Nomura, M Kopf, Y Katada, T Tanaka, M Suemura, T Kishimoto
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 14 Pg. 8222-6 (Jul 07 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9653168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• Interleukin-6
• Lymphotoxin-alpha
• RNA, Messenger

Topics

• Animals
• Arthritis, Rheumatoid (immunology, pathology, physiopathology)
• Gene Expression Regulation (immunology)
• Interleukin-1 (immunology)
• Interleukin-6 (genetics, immunology)
• Lymphotoxin-alpha (immunology)
• Mice
• Mice, Knockout
• RNA, Messenger (biosynthesis, immunology)