Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease

Abstract

SSc-ILD (scleroderma associated interstitial lung disease) is a complex rheumatic disease characterized in part by immune dysregulation leading to the progressive fibrotic replacement of normal lung architecture. Because improved treatment options are sorely needed, additional study of the fibroproliferative mechanisms mediating this disease has the potential to accelerate development of novel therapies. The contribution of innate immunity is an emerging area of investigation in SSc-ILD as recent work has demonstrated the mechanistic and clinical significance of the NLRP3 inflammasome and its associated cytokines of TNFα (tumor necrosis factor alpha), IL-1β (interleukin-1 beta), and IL-18 in this disease. In this review, we will highlight novel pathophysiologic insights afforded by these studies and the potential of leveraging this complex biology for clinical benefit.

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

“…These findings suggest that the NLRP3 inflammasome is involved in the pathogenesis of RA-ILD. Similarly, the aberrant activation of the NLRP3 inflammasome is observed in scleroderma-associated ILD [ 121 , 122 ]. Ramos-Martinez and colleagues demonstrated the enhanced activity of the NLRP3 inflammasome in the lungs of patients with anti-synthetase syndrome [ 123 ].…”