Interleukin-18 is associated with the presence of interstitial lung disease in rheumatoid arthritis: a cross-sectional study

Matsuo, Takashi; Hashimoto, Motomu; Ito, Isao; Kubo, Takeshi; Uozumi, Ryuji; Furu, Moritoshi; Ito, Hiromu; Fujii, Tomoyuki; Tanaka, Masao; Terao, Chikashi; Kono, Hajime; Mori, Masato; Hamaguchi, Mika; Yamamoto, Wataru; Ohmura, Koichiro; Morita, Satoshi; Mimori, Tsuneyo

doi:10.1080/03009742.2018.1477989

Cited by 25 publications

(18 citation statements)

References 39 publications

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“…Though the definite correlation between disease activity and ILD has not been elucidated, abnormal release of some inflammatory cytokines might be the culprit behind the scene. Studies have shown that RA-ILD is associated with the increase of various cytokines, including IL-33 and IL-18 (25,26). In this study, we showed that the increase of serum IL-11 was related to both the disease activity of RA and RA-ILD, indicating that IL-11 might exert an upstream role in the development of arthritis and ILD in RA patients.…”

Section: Discussionsupporting

confidence: 56%

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis

Wang

Zhu

Ren

et al. 2022

Clinical and Experimental Rheumatology

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ObjectiveTo investigate the association of serum with disease activity and occurrence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). MethodsOne hundred and six RA patients were included, including 31 with ILD. All patients were divided into two groups according to the 28-joint Disease Activity Score (DAS28), active-disease group (DAS28>3.2) and target-achieved group (DAS28≤3.2). Serum IL-11 was detected by ELISA. Serum autoantibodies [anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF)], inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)], and complete blood count were measured with routine methods. Results Serum IL-11 was upregulated in RA patients compared with healthy controls (HC), and increased more significantly in patients with ILD (RA-ILD) than patients without ILD (RA-nonILD). In both RA-ILD and RA-nonILD patients, serum level of IL-11 was higher in the active-disease group than that in the target-achieved group. Pearson correlation analysis confirmed that IL-11 was positively correlated with DAS28. No significant correlation was found between serum level of IL-11 and ACPA or RF. IL-11 was positively correlated with ESR and CRP levels and PLT count in RA patients. Conclusion IL-11 was found to be involved in the development of arthritis and ILD in RA patients, and might constitute a potential target for the treatment of RA-ILD.

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Section: Discussionsupporting

confidence: 56%

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis

Wang

Zhu

Ren

et al. 2022

Clinical and Experimental Rheumatology

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“…Chen et al 106 Interleukin-18 Matsuo et al 107 Interleukin-13 Hussein et al 109 Soluble programmed death-ligand 1 Wu et al 108 Matrix metalloproteinase-1, tissue inhibitors of metalloproteinases-1, osteopontin, soluble interleukin-2 receptor α, and interleukin-1 receptor antagonist…”

Section: Ra-ild Aodild Referencesmentioning

confidence: 99%

Biomarkers for interstitial lung disease and acute-onset diffuse interstitial lung disease in rheumatoid arthritis

Furukawa

Oka

Higuchi

et al. 2021

Therapeutic Advances in Musculoskeletal

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Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.

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“…A recent report has shown that active RA is associated with an increased risk for developing RA-ILD, with a hazard ratio of 2.22 for patients with moderate/high disease activity compared with those with LDA or in remission [ 218 ], thus providing the link with systemic inflammation, of which IL-6 is a key driver. However, while elevated levels of serum IL-6 (> 7.67 pg/ml) have been shown to be predictive of negative outcomes in ILD associated with systemic sclerosis (SSc-ILD) [ 219 ], and elevated serum interleukin-18 levels have recently been shown to be associated with the presence of ILD in patients with RA [ 220 ], there is a paucity of research investigating the role of IL-6 in RA-ILD [ 221 , 222 ].…”

Section: Il-6 Beyond the Joint: Common Comorbidities Of Ramentioning

confidence: 99%

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

Favalli

2020

Rheumatol Ther

100

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Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disorder involving inflammation and progressive destruction of the joints, affecting up to 1% of the population. The majority of patients with RA have one or more comorbid conditions, the most common being cardiovascular disease, osteoporosis, and depression, the presence of which are associated with poorer clinical outcomes and lower healthrelated quality of life. RA pathogenesis is driven by a complex network of proinflammatory cells and cytokines, and of these, interleukin-6 (IL-6) plays a key role in the chronic inflammation associated with RA. Through cell signaling that can be initiated by both membrane-bound and soluble forms of its receptor, IL-6 acts both locally to promote joint inflammation and destruction, and in the circulation to mediate extra-articular manifestations of RA, including pain, fatigue, morning stiffness, anemia, and weight loss. This narrative review describes the role of IL-6 in the pathogenesis of RA, its comorbidities, and extra-articular systemic manifestations, and examines the effects of the IL-6 receptor inhibitors sarilumab and tocilizumab on clinical endpoints of RA, patient-reported outcomes, and common comorbidities and extra-articular manifestations.

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Interleukin-18 is associated with the presence of interstitial lung disease in rheumatoid arthritis: a cross-sectional study

Cited by 25 publications

References 39 publications

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis

Biomarkers for interstitial lung disease and acute-onset diffuse interstitial lung disease in rheumatoid arthritis

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

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