Plasma Cytokine Profiling Reveals Differences between Silicotic Patients with Simple Silicosis and Those with Progressive Massive Fibrosis Caused by Engineered Stone

Abstract

Engineered stone silicosis has become an occupational epidemic disease that progresses rapidly to progressive massive fibrosis with respiratory failure and death, and there is no effective treatment. Silica deposition in the lung triggers a series of inflammatory reactions with the participation of multiple cytokines and cellular mediators whose role in the development and progression of the disease is largely unknown. We hypothesized that differences in plasma cytokine levels exist between patients diagnosed with simple silicosis (SS) and patients diagnosed with progressive massive fibrosis (PMF). Plasma samples from 91 ES silicosis patients, diagnosed and classified by chest radiography and/or high-resolution computed tomography with SS (n = 53) and PMF (n = 38), were assayed by multiplex assays for levels of 34 cytokines. Additionally, a healthy volunteer control group (n = 22) was included. Plasma levels of a high number of cytokines were significantly higher in subjects with silicosis than in healthy control subjects. Moreover, the levels of IL-1RA, IL-8, IL-10, IL-16, IL-18, TNF-α, MIP-1α, G-CSF and VEGF were significantly elevated in PMF compared to SS patients. This study shows that plasma cytokine levels differ between healthy people and silicosis patients, and some of them are also significantly elevated in patients with PMF compared with patients with SS, which could indicate their involvement in the severity of the disease, be considered as biomarkers and could be explored as future therapeutic targets for the disease.

Physiology and Biomarkers for Surveillance of Occupational Lung Disease

“…Of the biomarkers, ACE, LDH, and fibrinogen correlated with increasing disease severity and a combination of different biomarkers was required to predict progression with satisfactory accuracy. 104 Different techniques including multiplex assay cytokine profiling have also been applied, revealing that pro-inflammatory cytokines levels (IL-1β, IL-6, IL-7, IL-8, IL-16, IL-17A, IL-33, and TNF-α) distinguished between silica-exposed and control subjects even 6 years after removal from exposure. 104 A Th-2 response was predominant.…”

“…104 Different techniques including multiplex assay cytokine profiling have also been applied, revealing that pro-inflammatory cytokines levels (IL-1β, IL-6, IL-7, IL-8, IL-16, IL-17A, IL-33, and TNF-α) distinguished between silica-exposed and control subjects even 6 years after removal from exposure. 104 A Th-2 response was predominant. No doubt longitudinal studies will follow in this field and have real potential for improving methods of assessing disease progression, especially when combined with other biomarkers.…”