Analysis of serum interleukin(IL)‐1α, IL‐1β and IL‐18 in patients with systemic sclerosis

Abstract

Objectives Systemic sclerosis ( SS c) is an autoimmune disease characterised by fibrosis, vascular dysfunction and immune dysregulation. The pathogenesis of SS c remains poorly understood, although studies have indicated a role for the innate immune response. Methods Here, we measured serum interleukin ( IL )‐1α, IL ‐1β and IL ‐18 levels in 105 SS c patients and 47 healthy controls ( HC ) and analysed them with respect to multiple clinical parameters. Results Serum IL ‐18 concentrations were significantly higher in SS c patients than in HC , while no significant differences in concentrations of IL ‐1α and IL ‐1β were observed between SS c and HC . In both SS c and HC serum, IL ‐1α and IL ‐1β were positively correlated, while in SS c, both cytokines negatively correlated with IL ‐18. Serum IL ‐18 was significantly negatively correlated with both carbon monoxide transfer coefficient ( KCO ) and diffusing capacity of the lungs for carbon monoxide ( DLCO ). Serum IL ‐1β was positively correlated with the modified Rodnan skin score ( mRSS ), particularly in patients with limited subtype. DLCO , KCO and tricuspid regurgitation ( TR ) velocity were significantly higher in patients with high serum IL ‐1β. Serum IL ‐1α was significantly lower in SS c patients with low KCO and positively correlated with KCO . SS c patients with high serum IL ‐1α concentrations were more likely to have digital ulcers. Conclusions Our data suggest that these IL ‐1 family cytokines may have different roles in the pathogenesis of SS c fibrotic complications.

New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases

“…For example, some studies have indicated a significant increase in the content of caspase-1 in the skin tissue of SSc patients [160], while the level of caspase-1 in peripheral blood is significantly decreased [161]. In addition, Emily Lin et al found a lack of significant alteration in the level of IL-1β in the serum of SSc patients [162], while Y.-J. Zhanget al showed a significant increase [163].…”

“…Furthermore, the levels of NLRP3-related cytokines in SSc patients are closely correlated with certain clinical indicators. High levels of IL-18 in the serum indicate poor pulmonary function in patients, while high levels of IL-1β in skin tissue indicate severe skin fibrosis [160] and relatively better lung function [162]. However, there are also studies that refute the clinical predictive value of IL-1β levels in the serum [163].…”

Current Update on the Role of Inflammation in the Pathogenesis of SSc

“…This can be seen from a study they conducted on model mice with IL-18 deficiency, which experienced more severe fibrosis than wild-type mice. Another study by Kim et al showed that IL-18 downregulation occurs in human dermal fibroblasts which also indicates an anti-fibrotic effect of IL-18 on SSc, so that the actual role of IL-18 as a pro-fibrotic or anti-fibrotic still requires further research [41,42].…”

The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis

“…In addition, the serum level of IL-1α in SSc is controversial. Lin et al reported that SSc patients with high serum IL-1α concentrations were more likely to have digital ulcers (24). These data emphasize the need for further research to determine the role of IL-1α in SSc pathogenesis, particularly in obliterative vasculopathy.…”