Interleukin 22, a Potential Therapeutic Target for Rheumatoid Arthritis

Xie, Qiang; Wang, Shi‐Cun; Li, Jun

doi:10.3899/jrheum.120757

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…It is related to osteoclastogenesis by positively regulating the expression of Receptor Activator of Nuclear factor kappa-Β ligand (RANKL) mediated via Mitogen Activated Protein Kinase (MAPK) and Factor Nuclear kappa B - p38 MAPK/NF-κB and JAK-2/STAT-3 - signaling pathways [ 46 ]. But at the same time CD4 + Th22 cells are also related to the pathogenesis of RA, contributing to the worsening of this disease [ 47 ] by promoting the proliferation of synoviocytes [ 48 ], and may become a therapeutic target soon [ 49 - 51 ]. Few studies have correlated the levels of IL-22 with the RA severity and possible treatments to reduce this cytokine production [ 40 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients

Cardoso

Matias

Dantas

et al. 2018

TORJ

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Background:Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH.Objective:It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients.Methods:Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich.Results:Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition.Conclusion:PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.

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Section: Discussionmentioning

confidence: 99%

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients

Cardoso

Matias

Dantas

et al. 2018

TORJ

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“…However, IL‐22 is recognized as a pathogenic factor in the process of psoriasis . Similarly, IL‐22 has also been found to play a pro‐inflammatory role in collagen‐induced arthritis in C57BL/6 mice and RA . Thus, IL‐22 has both pathogenic and protective property in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Decreased Plasma IL‐22 Levels and Correlations with IL‐22‐Producing T Helper Cells in Patients with New‐Onset Systemic Lupus Erythematosus

2014

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Interleukin-22 (IL-22) and IL-22-producing T helper (Th) cells are involved in the pathogenesis of autoimmune diseases. However, the roles of IL-22 and IL-22-producing T helper cells in systemic lupus erythematosus (SLE) remain unclear. Plasma levels of IL-22 were measured in 41 patients with SLE (19 new-onset and 22 relapsing patients) and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the percentages of CD4 + IFN-c + (Th1), CD4 + IL-17 + (Th17) and CD4 + IFN-c À IL-17 À IL-22 + (Th22) cells in peripheral lymphocytes were determined by flow cytometry, and plasma IL-22 autoantibodies were detected by ELISA in 19 new-onset SLE patients and 20 healthy controls. Plasma IL-22 levels in new-onset SLE patients were significantly decreased compared with relapsing SLE patients and healthy controls. After treatment with prednisone and hydroxychloroquine, the levels of plasma IL-22 in new-onset SLE patients were obviously increased but still lower than healthy controls. There was a positive correlation between plasma IL-22 levels and the percentages of Th22 cells, but not Th1 and Th17 cells. Moreover, plasma IL-22 levels as well as peripheral Th17 and Th22 cells correlated with SLE disease activity index (SLEDAI) scores and erythrocyte sedimentation rate (ESR). High frequencies of plasma IL-22 autoantibodies were detected in new-onset SLE patients. However, IL-22 levels did not correlate with IL-22 autoantibody. Decreased plasma IL-22 levels and correlation with Th22 cells may be distinct features in new-onset SLE. Moreover, IL-22 and Th22 cell correlated with SLE disease activity.

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“…These cytokines feed another positive loop amplifying the Th17 response in an autocrine manner [ 50 , 57 ]. IL-22 seems to be crucially involved in the pathogenesis of psoriasis and RA [ 58 , 59 ] whereas IL-26 most likely contributes to the pathogenesis of intestinal inflammation [ 60 ].…”

Section: Th17-cellsmentioning

confidence: 99%

Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

et al. 2017

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A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases.

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Interleukin 22, a Potential Therapeutic Target for Rheumatoid Arthritis

Cited by 7 publications

References 12 publications

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients

Decreased Plasma IL‐22 Levels and Correlations with IL‐22‐Producing T Helper Cells in Patients with New‐Onset Systemic Lupus Erythematosus

Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

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