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

Abstract

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.

Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies

“…In conclusion, serum IL-18 was strikingly elevated in DM patients, associated particularly with disease activity and ILD complications. A similar study was conducted by Yang et al [78], showing the same results for DM-DM with ILD; however, no higher serum IL-18 levels were observed in patients with PM compared with controls.…”

“…(ii) Localised in inflammatory cells and capillaries in IIM patients [76]. (iii) High serum levels in DM/DM with interstitial lung disease [77,78] and PM [77].…”

The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies

“…Previous studies reported that ferritin was produced by macrophages [26] and correlated with lung function parameters and survival [27]. IL-18 was also secreted by macrophages [28], elevated in DM-ILD compared with DM without ILD [29], and correlated with the severity of pulmonary disease [30]. Together, these studies point to the importance of macrophages in the development and progression of CTD-ILD.…”

Biomarkers in Adult Dermatomyositis: Tools to Help the Diagnosis and Predict the Clinical Outcome

“…Several studies [47–50] have found IL-18 to be elevated in the serum of DM or CADM compared to HD. IL-18 was correlated with ferritin [48] and clinical activity scores [49, 50]. Concerning interstitial lung disease (ILD), Gono et al [48] and Yang et al [49] found that IL-18 was higher in DM-associated ILD (DM-ILD) compared to DM without ILD but no difference was found between RP-ILD compared to non-RP-ILD [23, 51].…”

“…IL-18 was correlated with ferritin [48] and clinical activity scores [49, 50]. Concerning interstitial lung disease (ILD), Gono et al [48] and Yang et al [49] found that IL-18 was higher in DM-associated ILD (DM-ILD) compared to DM without ILD but no difference was found between RP-ILD compared to non-RP-ILD [23, 51]. Zou et al [52] confirmed these results in CADM neutrophils: they found an increase of IL-18 mRNA in CADM patients compared to classical DM (cDM) and HD.…”