Blood Monocyte Subsets are Dysregulated and Respond with High IL-6 Secretion in Patients with Systemic Sclerosis

Abstract Background Most of the blood monocytes are classical monocytes (CM), minor subpopulations are intermediate monocytes (IM) and non-classical monocytes (NCM). CD56+ monocytes are a subpopulation of CM. Aim of the study was to analyze monocyte subpopulations in Systemic Sclerosis (SSc) patients and to evaluate their cytokine production potential. Methods 25 SSc patients and 16 age-matched healthy controls were included in the study. Monocyte subpopulations were analyzed by flow cytometry (antibody staining of CD14, CD16, CD56). Magnetic bead separation was used to isolate monocytes. The cells were stimulated with TLR4 ligand LPS and TLR8 ligand ssRNA40 and cytokines were measured by ELISA. Results The absolute number of circulating monocytes was significantly increased in SSc patients compared to healthy controls (684/μl ± 61 vs. 512/μl ± 38, p=0.033). Calculated absolute number of CM and CD56+ monocytes was not different between SSc patients and controls. In contrast, the calculated absolute numbers of IM (72/μl ± 13 vs. 32/μl ± 5, p=0.0003) and NCM was increased in SSc patients compared to controls (97/μl ± 12 vs. 45/μl ± 8, p=0.0011). The cytokine response of SSc monocytes to TLR4 ligand LPS was equal to control monocytes but SSc monocytes produced significantly more IL-6 in response to TLR8 ligand ssRNA40 than control monocytes. In addition, SSc monocytes already secrete IL-6 without further stimulation. IL-6 was also increased in the serum of SSc patients compared to healthy controls. Conclusion Total monocytes are expanded in the blood of SSc patients, and this increase is caused by an expansion of IM and NCM. The monocytes might contribute to the presence of IL-6 in SSc patients due to their increased potential to secrete this cytokine.