Mr. Swart, Ms Alcorn, and Dr. Tocker own stock and/or hold stock options in Amgen.
Interferon-γ regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17
Article first published online: 28 MAR 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 4, pages 1145–1151, April 2007
How to Cite
Chu, C.-Q., Swart, D., Alcorn, D., Tocker, J. and Elkon, K. B. (2007), Interferon-γ regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17. Arthritis & Rheumatism, 56: 1145–1151. doi: 10.1002/art.22453
- Issue published online: 28 MAR 2007
- Article first published online: 28 MAR 2007
- Manuscript Accepted: 12 DEC 2006
- Manuscript Received: 26 SEP 2006
- NIH. Grant Number: AR-050772
- NIH. Grant Number: T32
- Richard and Linda Carson Fellowship Grant
The enhanced expression of experimental arthritis in the absence of interferon-γ (IFNγ) suggests that IFNγ suppresses arthritis. Interleukin-17 (IL-17) is a pivotal T cell cytokine in arthritis, and in vitro studies have indicated that IFNγ suppresses IL-17 production. We undertook this study to test the hypothesis that resistance to collagen-induced arthritis (CIA) in C57BL/6 (B6) mice is regulated by IFNγ-mediated suppression of IL-17.
Wild-type (WT) B6 mice, IFNγ-knockout (KO) B6 mice, and DBA/1 mice were immunized with type II collagen (CII) in Freund's complete adjuvant (CFA). Lymphocytes from immunized mice were analyzed for cytokine production ex vivo by intracellular staining or restimulation with CII and enzyme-linked immunosorbent assays. In vivo blockade of IL-17 was achieved with an anti–IL-17 monoclonal antibody (mAb).
CII restimulation of T cells from CII/CFA-immunized mice resulted in an ∼5-fold increase in IL-17 production in IFNγ-KO B6 mice compared with WT B6 mice. Neutralization of IFNγ increased IL-17 production in WT B6 mice, and neutralization of IL-4 had a synergistic effect. Interestingly, the prototypical CIA-susceptible strain DBA/1 also demonstrated a high IL-17 and a low IFNγ cytokine profile compared with WT B6 mice. Administration of the anti–IL-17 mAb attenuated arthritis in DBA/1 mice and almost completely prevented expression of arthritis in IFNγ-KO B6 mice.
These results indicate that sensitivity of IFNγ-deficient B6 mice to CIA is associated with high IL-17 production and that this cytokine is required for expression of arthritis in this strain.