Suppression of collagen-induced arthritis by natural killer T cell activation with OCH, a sphingosine-truncated analog of α-galactosylceramide
Version of Record online: 9 JAN 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 1, pages 305–313, January 2004
How to Cite
Chiba, A., Oki, S., Miyamoto, K., Hashimoto, H., Yamamura, T. and Miyake, S. (2004), Suppression of collagen-induced arthritis by natural killer T cell activation with OCH, a sphingosine-truncated analog of α-galactosylceramide. Arthritis & Rheumatism, 50: 305–313. doi: 10.1002/art.11489
- Issue online: 9 JAN 2004
- Version of Record online: 9 JAN 2004
- Manuscript Accepted: 4 SEP 2003
- Manuscript Received: 3 APR 2003
- Grant-in-aid for Scientific Research from the Japanese Society for the Promotion of Science. Grant Number: (B)14370169
- Uehara Memorial Foundation
- Naito Foundation
- Organization for Pharmaceutical Safety and Research
OCH, a synthetic analog of α-galactosylceramide with a truncated sphingosine chain, stimulates natural killer T (NKT) cells to produce predominantly Th2 cytokines. Thus, OCH may be a potential agent for the treatment of Th1-mediated autoimmune diseases. This study was designed to evaluate the protective effects of OCH on collagen-induced arthritis (CIA) in mice.
Mice were immunized with type II collagen (CII) and injected intraperitoneally twice per week with OCH, before or after the onset of CIA. They were monitored to assess the effect of OCH treatment on the severity of disease. Anti-CII antibodies and cytokine production were measured by enzyme-linked immunosorbent assay. Expression of cytokine genes was determined by quantitative reverse transcriptase–polymerase chain reaction.
OCH inhibited CIA in wild-type C57BL/6 (B6) mice but not in NKT-deficient mice. OCH suppressed CIA in SJL mice, which are prone to autoimmune diseases and have a deficiency in the number and function of NKT cells which is similar to that in patients with autoimmune diseases, even after disease has already developed. Disease protection conferred by OCH correlated with its ability to selectively induce Th2 cytokine production mediated by NKT cells and to promote collagen-specific Th2 responses. Neutralization of interleukin-4 (IL-4) or IL-10 with monoclonal antibodies abolished disease protection by OCH, indicating a critical role for these cytokines.
Taken together, our findings suggest that OCH holds possibilities as a therapeutic agent for autoimmune diseases such as rheumatoid arthritis.