Background/Purpose:  Three different subsets of monocytes, CD14^brightCD16- (classical), CD14^brightCD16+ (intermediate), and CD14^dimCD16+ (nonclassical) have been recently identified. It has been reported that CD14^brightCD16+ monocytes are increased in rheumatoid arthritis (RA). However, the role of each monocyte subset in the pathogenesis of RA is still unclear. The purpose of this study was to investigate the association of CD14^brightCD16+ monocytes with RA.

Methods:  The study enrolled 35 untreated RA patients and 14 healthy volunteers. DAS28-ESR was evaluated and peripheral blood samples were obtained at baseline and following 12 weeks after methotrexate treatment. The three subsets of peripheral blood monocytes were analyzed by flow cytometry. Serum levels of cytokines were measured at baseline of the patients. CD14^brightCD16- monocytes were isolated and cultured in vitro with indicated cytokines for 14 hours and assessed in CD16 induction.

Results:  The proportion of CD14^brightCD16+ monocytes and serum levels of interleukin-6 (IL-6), IL-8, and IL-10 were increased in RA patients at baseline compared to healthy controls. The degree of disease activity of RA positively correlated with the proportion of CD14^brightCD16+ monocytes, while proportion of CD14^brightCD16- monocytes had negative correlation. When isolated CD14^brightCD16- monocytes were stimulated with IL-6, IL-8, and IL-10, IL-10 was the only cytokine that remarkably induced CD16 expression on the cells. Moreover, addition of anti-IL-10 receptor blocking antibody significantly suppressed CD16 expression on CD14^brightCD16- monocytes compared with that of control antibody.

Conclusion:  The proportion of CD14^brightCD16+ monocytes positively correlated with RA disease activity and CD14^brightCD16+ monocytes were induced from CD14^brightCD16- monocytes by IL-10 but not by other cytokines upregulated in the sera from RA patients. Our results suggest that CD14^brightCD16+ monocytes are possibly involved in the pathogenesis of RA and IL-10 may be a key cytokine that regulates CD14^brightCD16+ monocytes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-circulating-cd14brightcd16-intermediate-monocytes-are-regulated-by-interleukin-10-in-patients-with-rheumatoid-arthritis/