Inflammatory Response of Monocytes/Macrophages in Patients with Systemic Sclerosis

Abstract

Background: Investigation of the inflammatory response of immune cells is a current focus of research on autoimmune disorders. The aim of this study was to evaluate the inflammatory status of monocytes/macrophages in systemic sclerosis (SSc). Methods: The study included 35 SSc and 25 healthy participants. The secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA) in primary cultures of monocytes/macrophages after stimulation with lipopolysaccharide (LPS) on day 1 and on day 6 of incubation. Impaired tolerance of the immune response was characterized by increased secretion of the inflammatory mediators in response to restimulation. Results: Basal secretion of all cytokines was significantly higher in SSc patients compared to healthy individuals. The secretion of TNF-α, IL-1β and IL-6 after the initial LPS stimulation, and secretion of IL-1β, MCP-1, IL-6, IL-8 after LPS restimulation, was significantly higher in the SSc group. Eleven SSc patients (31%) showed impaired immune tolerance in terms of MCP-1 secretion. These patients were significantly younger and had a higher level of anti-topoisomerase I (anti-Scl70) antibodies compared to SSc patients with immune tolerance. Conclusions: This study revealed pro-inflammatory activation and impaired immune tolerance in monocytes/macrophages from SSc patients. The violation of immune response in terms of MCP-1 secretion may be an important factor in the development of chronic inflammation in SSc. MCP-1 may thus be a potential therapeutic target for novel SSc treatment strategies.

Keywords

• systemic sclerosis
• monocytes
• macrophages
• inflammation
• cytokines