Categories:   LabSHOTS News Technical Notes

Cytokines & Chemokines in Disease: Rheumatoid Arthritis

Cytokines and chemokines are key modulators of immune responses and play diverse roles in inflammatory diseases. Here, we discuss the role of specific cytokines and chemokines in rheumatoid arthritis (RA).

Chondrex, Inc. is committed to enabling inflammatory research worldwide by providing a variety of animal models and detection assays for your study needs. Please visit our Cytokine & Chemokine Detection ELISA Kits page for a complete list of the ELISA kits we offer and suggested animal models for your research needs.

Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent inflammation in the joints leading to pain and disability. The fundamental importance of cytokines in RA progression is overwhelming, with TNF-?, IL-6 and IL-1 being the most influential cytokines. IL-6 and TNF-? inhibitors are currently used as treatment options for patients with severe RA, further supporting their importance (1,2). Recent journals have shown that cytokine/chemokine detection, in combination with other serological tests, can be used to determine RA progression in a clinical setting. During the pre-clinical phase of RA, IL-17 and CXCL8 are upregulated, potentiating pro-inflammatory cytokine signaling. If left untreated, this chronic inflammation will lead to cartilage degradation and bone erosion (1,2).

In later stages of RA, TNF-?, IL-6 and IL-1 are upregulated, stimulating increased expression of adhesion molecules and an increase in the iNOS/ROS ratio of synovial fluids (1,2). Other studies have found that there is impaired production of IL-10 and IL-13 in RA patients, hindering anti-inflammatory pathways (3). Furthermore, CCL2 levels tend to be elevated in RA and are strongly associated with macrophage infiltration. Macrophages then generate CXCL1 and CXCL8 that promote neutrophil recruitment, leading to CXCL2 production. CXCL2 is known to amplify neutrophil and macrophage chemokine release. Subsequently, T-Cells, B-Cells and other immune cells respond to the chemokine signaling and enhance inflammation (4,5).

To counterbalance the overwhelming pro-inflammatory response in RA, researchers have focused on the role of anti-inflammatory cytokines/chemokines as therapeutic options for attenuating the inflammatory process in RA. Upregulation of IL-4 and IL-13 by T-Helper type 2 (Th2) cells reduces the production of IL-1? and TNF-? elicited by activated macrophages located in synovial tissue. Post-translational modification of chemokines, in particular citrullination, is another possible mechanism that can be utilized therapeutically. Citrullination is the process by which peptidylarginine deiminases (PADs) convert Arginine to Citrulline which leads to an alteration on the chemokine activity and reduce chemotaxis, rendering the process anti-inflammatory (4,5). 

A recent study published in the journal Science Translational Medicine tested the effectiveness of the highly inflammatory, erythrocyte-specific antibody Ter119 on RA inflammatory response. The group used Chondrex, Inc.’s Collagen Antibody Induced Arthritis (CAIA) model in mice and detected an upregulation of various cytokines and chemokines by ELISA, including CCL2, TNF-?, CXCL10, CXCL5 and CCL5. When CAIA mice were treated with Ter119, inflammatory arthritis was ameliorated or prevented. In addition, there was a dose-dependent decreases in the inflammatory cytokines/chemokines CCL2, TNF, CXCL5, and CCL5 demonstrating a significant decline in chemokine/cytokine secretion in the joints (6).

Publications Utilizing Chondrex, Inc. RA Models for Cytokine Assessment


  1. L. Ridgley, A. Anderson, A. Pratt, What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol 30, 207-214 (2018).
  2. S. Mateen, A. Zafar, S. Moin, A. Khan, S. Zubair, Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta 455, 161-71 (2016).
  3. Z. Chen, A. Bozec, A. Ramming, G. Schett, Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol 15, 9-17 (2019).
  4. N. Elemam, S. Hannawi, A. Maghazachi, Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis. Immunotargets Ther 9, 43-56 (2020).
  5. Y. Miyabe, J. Lian, C. Miyabe, A. Luster, Chemokines in rheumatic diseases: pathogenic role and therapeutic implications. Nat Rev Rheumatol 15, 731-746 (2019).
  6. A. Crow, R. Kapur, S. Koernig, I. Campbell, C. Jen, et al., Treating murine inflammatory diseases with an anti-erythrocyte antibody. Sci Transl Med 11, eaau8217 (2019).


Join Our Mailing List