Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease

Gono, Takahisa; Kawaguchi, Yasushi; Sugiura, Tomoko; Ichida, Hisae; Takagi, Kae; Katsumata, Yasuhiro; Hanaoka, Masanori; Okamoto, Yuko; Ota, Yukiko; Yamanaka, Hisashi

doi:10.1093/rheumatology/keq196

Cited by 56 publications

(44 citation statements)

References 11 publications

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“…8,9 In our study, serum IL-18 level was found to be significantly elevated in patients with DM when compared to those with PM or healthy individuals. The level was particularly high in DM patients with severe disease, in agreement with a previous report by Gono et al 11 However, we did not observe any significant difference in IL-18 level between the PM and control groups. This finding differs from a previous study that demonstrated increased IL-18 in patients with PM.…”

Section: Discussionsupporting

confidence: 93%

“…This is consistent with a previous study that also found no difference in serum IL-18 in PM patients with or without accompanying ILD. 11 Our results suggest that IL-18 plays greater roles in the induction of ILD in DM when compared to PM patients, and IL-18 can be used as a serum marker for DM patients with ILD.…”

Section: Discussionmentioning

confidence: 58%

“…8,9 Recent studies showed increased serum IL-18 level in patients with different clinical manifestations of DM/PM, 10 especially in those with ILD, 11 further demonstrating the activation of Th1 immune response in idiopathic inflammatory myopathies. However, the clinical consequences and pathomechanism of elevated serum IL-18 level are still poorly understood.…”

mentioning

confidence: 96%

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Serum Interleukin-18 Level is Associated With Disease Activity and Interstitial Lung Disease in Patients With Dermatomyositis

et al. 2017

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Objectives:This study aims to demonstrate the utilization of serum interleukin-18 (IL-18) level as a biomarker for disease activity and organ damage in patients with dermatomyositis (DM) or polymyositis (PM) using the Myositis Disease Activity Assessment Tool. Patients and methods: Forty-nine patients (13 males, 36 females) with idiopathic inflammatory myopathies were enrolled in the study. Patients were diagnosed with DM (n=33) or PM (n=16). Twenty age-and sex-matched healthy volunteers (9 males, 11 females) who were determined to be free of autoimmune disease were included as a control group. Disease activity and organ damage were assessed with Myositis Disease Activity Assessment Tool. Serum IL-18 level was measured with enzyme-linked immunosorbent assay and the differences between patient groups were determined. Results: The mean ages of DM or PM patients were 44 and 45, respectively. Interstitial lung disease (ILD) was found in 24 patients (48.98%), including 18 patients with DM (54.55%) and six patients with PM (37.5%). There was no significant difference of disease duration between DM patients (17.5±22.3 months) and PM patients (14.9±28.7 months). Serum IL-18 level in DM (669.2±528.1 pg/mL) was significantly higher than that in the control group (388.3±139.4 pg/mL, p=0.017), but no significant difference was observed between the PM and control group. IL-18 was significantly higher in DM patients with ILD (890.5±618.8 pg/mL) than in patients without ILD (403.8±84.8 pg/mL, p=0.003). It was significantly elevated in patients with severe disease activity (1001.7±694.2 pg/mL) than in those with moderate (485.3±102.2 pg/mL) or mild disease activity (421.0±270.2 pg/mL) (p=0.039). In DM patients, IL-18 was significantly correlated with global disease activity and disease activity in the skin, lung, and heart. Conclusion: Serum IL-18 level was higher in patients with DM and this was associated with disease activity and ILD complication. Thus, it can be used as a valuable serological marker for DM disease activity and ILD complication.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 58%

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Serum Interleukin-18 Level is Associated With Disease Activity and Interstitial Lung Disease in Patients With Dermatomyositis

et al. 2017

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“…Furthermore, IL-18 serum levels were found to be increased in DM patients and to decline as patients approached clinical remission [18]. A recent study showed that IL-18 serum levels are higher in DM patients with interstitial lung disease than those without it, and that IL-18, ferritin, and creatine kinase are all correlated [19]. Serum IL-18 levels were significantly higher in DM than in PM patients.…”

Section: Interleukin-18mentioning

confidence: 98%

“…Serum IL-18 levels were significantly higher in DM than in PM patients. The authors suggested that IL-18 may stimulate type 1 IFN-regulated chemokines and pDCs, which induce muscle inflammation in DM [19].…”

Section: Interleukin-18mentioning

confidence: 99%

Pathogenesis of Dermatomyositis: Role of Cytokines and Interferon

2011

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Dermatomyositis is a systemic autoimmune disease that primarily affects skeletal muscle, skin, and the lungs. Dermatomyositis is characterized by autoantibodies, tissue inflammation, parenchymal cell damage and death, and vasculopathy. This review focuses on recent advances regarding the role of cytokines and interferon in the pathogenesis of the disease. Evidence for the role of a particular cytokine is based on data showing dysregulated levels in tissue and/or blood; correlation with histopathologic or clinical markers of disease activity; and, rarely, clinical efficacy of targeted cytokine inhibitors. Many of the recent advances pertain to elucidation of the role of interferons in both muscle and skin disease in dermatomyositis. Although a great deal of progress has been made regarding the role of interferon in the disease, many critical questions remain unanswered.

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Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High‐Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis

Tsuji

Nakashima

Hosono

et al. 2020

Arthritis & Rheumatology

254

168

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Objective Interstitial lung disease (ILD) accompanied by anti–melanoma differentiation–associated gene 5 (anti–MDA‐5)–positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti–MDA‐5–positive DM patients with ILD. Methods Adult Japanese patients with new‐onset anti–MDA‐5–positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high‐dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6‐month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti–MDA‐5–positive DM patients with ILD who received step‐up treatment (high‐dose GC and stepwise addition of immunosuppressant). Secondary end points were 12‐month survival rate, adverse events, and changes in laboratory data. Results The combined immunosuppressive regimen group showed significantly higher 6‐month survival rates than the step‐up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti–MDA‐5 titers, serum ferritin levels, vital capacity, and chest high‐resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step‐up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. Conclusion A combined immunosuppressive regimen is effective for anti–MDA‐5–positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.

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Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease

Abstract: Serum IL-18 was strikingly elevated in patients with DM and was associated particularly with disease activity and ILD complication in DM.

Cited by 56 publications

References 11 publications

Serum Interleukin-18 Level is Associated With Disease Activity and Interstitial Lung Disease in Patients With Dermatomyositis

Serum Interleukin-18 Level is Associated With Disease Activity and Interstitial Lung Disease in Patients With Dermatomyositis

Pathogenesis of Dermatomyositis: Role of Cytokines and Interferon

Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High‐Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis

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