Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Abstract

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis (RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines (e.g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-γ at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA.

A comparison of multiplex suspension array large‐panel kits for profiling cytokines and chemokines in rheumatoid arthritis patients

“…The simplest explanation for these results is that because rituximab targets B-cells and because most of these elevated cytokines are macrophage and T-cell products, the levels of these cytokines were not affected by B-cell reductive therapy (25). Furthermore, because rituximab treatment was effective in patients (17) that were found to contain elevated immunomodulators in this study, the results may suggest that the observed elevation in cytokine levels mediated or supported B-cell activation and survival, which in turn could lead to a disease state that is more responsive to B-cell reductive therapy.…”

Human innate immunosenescence: causes and consequences for immunity in old age

“…The appropriate initiation and resolution of their inflammatory responses is crucial to the clearance of infections and the prevention of non-specific tissue damage leading to chronic inflammatory disease and frailty. That the function of these cells might be compromised by aging is indicated not only by the increased morbidity and mortality due to bacterial infections in the elderly [67,68], but also by the wealth of clinical data showing that age is an independent risk factor for the development of chronic inflammatory diseases which include a pathogenic role for neutrophils, for example rheumatoid arthritis [69,70]. …”

The effect of alpha asarone, olive oil, and dexamethasone on collagen-induced arthritis (CIA) in the mouse

“…IL-17 has multiple effects on many cells, including neutrophils, macrophages, fibroblasts, epithelial cells, endothelial cells and mesenchymal cells, deregulating transcription factors that are involved in the synthesis of pro-inflammatory cytokines (IL-1, IL-6, GMCSF, TNF), chemokines, and osteogenic factor (responsible for bone resorption). The combined effect of these molecules leads to inflammation and chronic destruction of the articulation [46][47][48]. However, although neutrophils may cause tissue damage after granule exocytosis, they may also participate in the process of tissue remodelling, and this latter possibility perhaps explains their presence in the CIA lesions of mice treated with alpha asarone.…”