Abstract
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). 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. 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. 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.
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