Disease Activity and Cytokine Production in Mitogen-Stimulated Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis

Abstract

<i>Objective:</i> To test whether there are differences in the levels and ratios of 6 pro- and 3 anti-inflammatory cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) subjects compared to controls. <i>Subjects and Methods:</i> 79 participants (42 seropositive RA patients and 37 healthy controls) were enrolled in this study. The production levels in mitogen-stimulated PBMCs of the 6 proinflammatory cytokines (IFN-γ, TNF-α, TNF-β, IL-8, IL-17, IL-18) and 3 anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed by ELISA using kits obtained from Immunotech SA. The ratios of pro- to anti-inflammatory cytokines were calculated for all participants. <i>Results:</i> There were significantly elevated levels of IL-8 and IL-10, and reduced levels of IFN-γ, IL-4, and IL-17 in mitogen-stimulated PBMC culture supernatants of RA subjects compared to controls. Of the 18 pro-/anti-inflammatory cytokine ratios, 3 ratios (TNF-α/IL13, IL-8/IL-4 and IL-8/IL-13) were significantly higher in RA patients compared to controls; and 6 were higher in controls (IFN-γ/IL-4; IFN-γ/IL-10; IFN-γ/IL-13; TNF-β/IL10; IL-17/IL-10; IL-18/IL-10). <i>Conclusions:</i>Activated PBMCs of RA patients, regardless of disease activity, showed higher-level production of IL-8 and IL-10 compared to controls; lower-level production of IFN-γ, IL-4, and IL-17; and elevated ratios of TNF-α/IL-13, IL-8/IL-4 and IL-8/IL-13.

Serum biochemical parameters and cytokine profiles associated with natural African trypanosome infections in cattle

“…The relevance of the balance between pro- and anti-inflammatory cytokines has been demonstrated in both infectious [41, 42] and non-communicable diseases [43, 44]. On this basis, the pro- to anti-inflammatory cytokine ratios were therefore assessed at basal levels and during infection.…”

Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes

“…Furthermore, the concentration of VEGF increased significantly during incubation with both synovial fluids, but the levels of VEGF even stayed at higher levels in the OA samples when compared to RA samples. It is known that growth factors play a pivotal role in the initiation and development of rheumatic joint diseases [14,15]. VEGF modulates angiogenesis, the proliferation and formation of new capillaries from an existing vascular network, and is highly involved in inflammatory processes.…”

“…Interleukins-6 and 8 (IL-6, IL-8) are pro-inflammatory and angiogenic cytokines, and are also potent chemoattractants for neutrophils. Various studies showed increased levels of IL-6 and IL-8 in peripheral blood mononuclear cells or bone marrow of RA patients [15]. In the pathogenesis of OA, pro-inflammatory cytokines like IL-6 and IL-8 also play an important role.…”

Silicon, a Possible Link between Environmental Exposure and Autoimmune Diseases: The Case of Rheumatoid Arthritis

“…This may indicate the relationship between the outcomes of exposure to asbestos and RA. [13, 14] The results of Song et al [15] in which TGF β -1 promotes the differentiation of synovial fibroblast to myofibroblast seem to support the above. This is the first step in the process that ends in tissue fibrosis [15].…”

“…For instance, asbestos stimulates the transcription of interleukin-8 (IL-8), which is the major neutrophil chemoattractant in the lung, and the transcription of transforming growth factor- β -1 (TGF β -1), an important mediator of hematopoietic differentiation, cellular chemoattraction, and stimulation of fibroblast and myofibroblast [11, 12]. Likewise, Uppal et al [13] found that activated peripheral blood mononuclear cells (PBMCs) of RA patients showed higher levels of IL-8 [13]. In addition, polymorphism in TGFB1 has been related to bone-erosive damage in these patients [14].…”