Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis

Filková, Mária; Vernerová, Zdeňka; Hulejová, Hana; Prajzlerová, Klára; Veigl, D; Pavelka, Karel; Vencovský, Jiří; Šenolt, Ladislav

doi:10.1016/j.cyto.2015.01.019

Cited by 45 publications

(37 citation statements)

References 35 publications

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“…In CIA, a mouse model of rheumatoid arthritis, IL‐35 gene transfer can result in a considerable increase in clinical scores for CIA, associated with a high Th17/T reg ratio in the spleen ; these findings are in accordance with the upregulation of IL‐35 at inflammatory sites as a pro‐inflammatory molecule in rheumatoid arthritis reported by Filková et al . . However, in Borrelia‐vaccinated and −infected mice, IL‐35 reportedly does not exert an anti‐inflammatory effect or reduce the severity of arthritis by inhibiting production of IL‐17 , which is in contrast with Li et al .…”

Section: Discussionmentioning

confidence: 67%

“…A member of the IL‐12 family, IL‐35 not only has an immunosuppressive function in autoimmune and/or autoinflammatory diseases, but also reportedly has pro‐ and/or anti‐inflammatory effects in diseases such as rheumatoid arthritis . In one study of patients with ulcerative colitis and Crohn disease, serum IL‐35 concentrations were found to be dramatically lower than in healthy individuals and to have a moderate negative correlation with Mayo scores in ulcerative colitis .…”

Section: Discussionmentioning

confidence: 99%

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Clinical significance of weak interleukin‐35 expression in patients with psoriasis

Liu

et al. 2018

Microbiology and Immunology

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In psoriasis, a chronic, recurrent, inflammatory skin disease, CD4+T cells and their related cytokines play an important role in its pathogenesis. The role of interleukin (IL)-35, an immunosuppressive cytokine involved in many autoimmune diseases, is unclear in the pathogenesis of psoriasis. This study evaluated IL-35 expression and clinical significance in psoriasis. Protein and mRNA levels of specified markers were measured by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. Results showed that plasma IL-35 concentrations were lower in patients with psoriasis than in healthy individuals (Z = -6.525, P < .0001). Ebi3 and p35 showed lower mRNA levels in peripheral blood mononuclear cells from patients with psoriasis than in healthy individuals (Z = -5.078, P < .0001, Z = -2.609, P = .009, respectively). The areas under the receiver-operating characteristic (ROC) curves of IL-35, Ebi3, and p35 for patients with psoriasis versus the control were 0.86, 0.78, and 0.64, respectively. Pearson correlation analysis showed that plasma IL-35 expression negatively correlated with interferon-gamma, tumor necrosis factor-alpha, levels of IL-23, -17, and -22, or the Psoriasis Activity and Severity Index and positively correlated with levels of transforming growth factor beta and IL-10 levels in patients with psoriasis. Summarily, IL-35 might mediate psoriasis pathogenesis by influencing the expression of Th1/Th17/T -related cytokines and might be a putative target in monitoring or treating psoriasis.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Clinical significance of weak interleukin‐35 expression in patients with psoriasis

Liu

et al. 2018

Microbiology and Immunology

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“…IL-35 was found to be higher in patients with treatment naïve early RA compared to those with established disease and to be reduced after 3 months treatment with glucocorticoids and conventional synthetic (cs) DMARDs [101]. IL-35 was found to be also higher in SF RA compared to PsA and control OA patients and correlated with higher disease activity, supporting a potential role of IL-35 in the pathogenesis of RA [101,102]. Moreover, TNF-α can induce the expression of both p35 and EBI3 subunits in FLS and MCs, and since the latter express both subunits of IL-35 receptor can secrete several pro-inflammatory molecules (IL-1β, IL-6 and MCP-1) upon IL-35 stimulation [102].…”

Section: Il-35mentioning

confidence: 75%

“…IL-35 was found to be also higher in SF RA compared to PsA and control OA patients and correlated with higher disease activity, supporting a potential role of IL-35 in the pathogenesis of RA [101,102]. Moreover, TNF-α can induce the expression of both p35 and EBI3 subunits in FLS and MCs, and since the latter express both subunits of IL-35 receptor can secrete several pro-inflammatory molecules (IL-1β, IL-6 and MCP-1) upon IL-35 stimulation [102]. Nakano et al reported that serum levels of IL-35 are decreased in RA patients, when compared with normal controls, mainly in patients with active disease, with an inverse correlation between serum IL-35 levels and the 28-joint disease activity score (DAS) based on CRP [103].…”

Section: Il-35mentioning

confidence: 83%

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

et al. 2017

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In recent years, the landscape of pro- and anti-inflammatory cytokines has rapidly expanded with the identification of new members proven to be involved at different extent in the pathogenesis of chronic immune mediated inflammatory diseases including rheumatoid arthritis (RA). The advance of our understanding of mediators involved in the pathogenesis of RA and in consequence, the development of novel targeted therapies is necessary to provide patients not responding to currently available strategies with novel compounds. The aim of this review article is to provide an overview on recently identified cytokines, emphasizing their pathogenic role and therapeutic potential in RA. A systematic literature review was performed to retrieve articles related to every cytokine discussed in the review. In some cases, evidence from animal models and RA patients is already consistent to move forward into drug development. In others, conflicting observation and the paucity of data require further investigations.Forty years after the discovery of IL-1, the landscape of cytokines is continuously expanding with increasing possibilities to develop novel therapeutic strategies in RA. Electronic supplementary material The online version of this article (10.1186/s41927-017-0001-8) contains supplementary material, which is available to authorized users.

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“…A recent study showed that recombinant human IL-35 cytokine could stimulate peripheral blood mononuclear cells (PBMCs) to produce IL-6 and IL-1β [32]. IL-6 could be produced by macrophages and the activated T lymphocytes [33].…”

Section: Resultsmentioning

confidence: 99%

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

Zou

Qin

et al. 2017

Oncotarget

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IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1β and IL-6. IL-1β stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.

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Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis

Cited by 45 publications

References 35 publications

Clinical significance of weak interleukin‐35 expression in patients with psoriasis

Clinical significance of weak interleukin‐35 expression in patients with psoriasis

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

IL-35 induces N2 phenotype of neutrophils to promote tumor growth

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