Interleukin 6 Plays a Key Role in the Development of Antigen-Induced Arthritis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 14; pp. 8222 - 8226
• Main Authors: Ohshima, Shiro, Saeki, Yukihiko, Mima, Toru, Sasai, Mitsuko, Nishioka, Katsuhiro, Nomura, Shintaro, Kopf, Manfred, Katada, Yoshinori, Tanaka, Toshio, Suemura, Masaki, Kishimoto, Tadamitsu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 07.07.1998; National Acad Sciences; The National Academy of Sciences
• Subjects: Animals; Arthritis; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Arthritis, Rheumatoid - physiopathology; Biological Sciences; Cartilage; Cell growth; Cytokines; Gene Expression Regulation - immunology; Histology; Immunization; Immunology; Interleukin-1 - immunology; Interleukin-6 - genetics; Interleukin-6 - immunology; Knee joint; Lymph nodes; Lymphotoxin-alpha - immunology; Mice; Mice, Knockout; Pathology; RNA, Messenger - biosynthesis; RNA, Messenger - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.14.8222

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-1β and tumor necrosis factor α , 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-1β or tumor necrosis factor α . 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.