Pro-inflammatory response of monocytes in systemic sclerosis

Objective: The investigation of inflammatory response of immune cells is one of the most actual trends in research of autoimmune disorders including SSc. This study was aimed to investigate the inflammatory cytokines secretion and to evaluate the pro-inflammatory status of blood-derived monocytes in SSc. Methods. The study included 35 SSc and 25 heathy participants. Secretion of inflammatory cytokines TNF-α a, IL1β, CCL2 and IL8 was measured by ELISA in primary culture of monocytes/macrophages after stimulation with LPS on day 1 and 6 of incubation to assess the pro-inflammatory activation and immune tolerance of monocytes. Impaired tolerance of immune response is characterized by increased secretion of inflammatory mediators in response to re-stimulation. Results. Basal secretion of TNF-α, IL1β, CCL2 and IL8 was significantly higher in SSc patients than in healthy subjects. After the first LPS-stimulation secretion of TNF-α and IL1β, but not CCL2 and IL8 was also higher in SSc group. In 24 hours after re-stimulation, the secretion of IL1β, CCL2 and IL8, but not TNF-α increased significantly in SSc group compared to healthy control. CCL2 secretion by re-stimulated monocytes was 1.8-fold higher than in cells without re-stimulation in SSc group, that was significantly different from healthy subjects. Conclusion. The study results demonstrate pro-inflammatory activation and impaired immune tolerance of monocytes in SSc. The violation of immune response in terms of CCL2 may be an important factor of the chronification of inflammation in SSc. Thus, CCL2 should be considered as therapeutic target for the development of immunomodulatory strategies for SSc treatment.