1529-0131/asset/olbannerleft.gif?v=1&s=897b81612b4ad6cae003112184adc709261d5f61)
1529-0131/asset/olbannerright.gif?v=1&s=04654f5ea3cbb01656383e0c0d04b16fd0a9a896)
Rheumatoid Arthritis Basic Science Studies
Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis
Article first published online: 7 JAN 2010
DOI: 10.1002/art.27186
Copyright © 2010 by the American College of Rheumatology
Additional Information
How to Cite
Kokkonen, H., Söderström, I., Rocklöv, J., Hallmans, G., Lejon, K. and Rantapää Dahlqvist, S. (2010), Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis & Rheumatism, 62: 383–391. doi: 10.1002/art.27186
Publication History
- Issue published online: 28 JAN 2010
- Article first published online: 7 JAN 2010
- Accepted manuscript online: 7 JAN 2010 12:00AM EST
- Manuscript Accepted: 2 OCT 2009
- Manuscript Received: 17 MAR 2009
Funded by
- Swedish Research Council. Grant Number: K2007-52X-20307-01-3
- King Gustaf V's 80-Year Fund
- Swedish Rheumatism Association
- University of Umeå
- European Community Sixth Framework Programme (project AutoCure)
- Abstract
- Article
- References
- Cited By
Abstract
Objective
To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA).
Methods
A nested case–control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system.
Results
The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1β [IL-1β], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-γ, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow–derived factors (IL-7, granulocyte–macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1α). The levels were particularly increased in anti–cyclic citrullinated peptide antibody– and rheumatoid factor–positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell–related cytokines, while chemokines, stromal cell–derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA.
Conclusion
Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell–related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.