Serum levels of interleukin‐18‐binding protein isoform a: Clinical association with inflammation and pulmonary hypertension in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a chronic autoimmune inflammatory disease characterized by extensive tissue fibrosis and various vascular complications. A wealth of evidence suggests the substantial contribution of pro-inflammatory cytokines to the development of SSc, but the role of interleukin (IL)-18 signaling in this disease still remains elusive. To address this issue, we herein determined serum levels of IL-18-binding protein isoform a (IL-18BPa), a soluble decoy receptor for IL-18, by enzyme-linked immunosorbent assay in 57 SSc patients and 20 healthy controls and evaluated their clinical correlation. Serum IL-18BPa levels were higher in SSc patients than in healthy controls, while comparable between diffuse cutaneous SSc and limited cutaneous SSc patients. Although serum IL-18BPa levels were not associated with dermal and pulmonary fibrotic parameters in SSc patients, there was a significant positive correlation between serum IL-18BPa levels and right ventricular systolic pressure estimated by echocardiography. Furthermore, in 24 SSc patients who underwent right heart catheterization, serum IL-18BPa levels positively correlated with mean pulmonary arterial pressure. As for systemic inflammatory markers, significant positive correlations of circulating IL-18BPa levels with erythrocyte sedimentation rate and C-reactive protein were noted. These results suggest that the inhibition of IL-18 signaling by IL-18BPa may be involved in the development of pulmonary vascular involvement leading to pulmonary hypertension and modulate the systemic inflammation in SSc.

Serum interleukin-18

“…[25,26] Serum IL-18 levels significantly increase during hypoxia caused by acute lung injury [27] and elevated IL-18 levels have been associated with the presence of systemic inflammation. [28] Our results showed that APACHE II was significantly lower in ARDS patients with high level of serum IL-18 than that with low IL-18. APACHE II was also significantly lower in the non-survival group than that in survival group.…”

Manifestation of echocardiography for dynamic change in right ventricular function and structure of patients with pulmonary hypertension

“…Realtime three-dimensional cardiac ultrasound effectively overcomes the limit of application range of two-dimensional ultrasound in clinical, and can directly make quantitative measurement of actual ventricular volume. This measurement has higher accurate and convenient measurement of irregular geometrical ventricular volume which can satisfy with accurate evaluation of right ventricular functions in clinical [11][12][13].…”

MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors

“…Furthermore, interleukin-18 (IL-18) Receptor 1 (IL-18R1) is a miR-26 target expressed by WBCs. Previous publications showed that IL-18 levels are altered in SSc patients [39,40] and that there is a positive correlation between serum IL-18 binding protein (IL-18BPa) levels and right ventricular systolic pressure [39].…”