Abstract
BackgroundRheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and ultimately disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from “outside the joint” can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. It is believed that IL-17 is involved in pathogenesis of RA. However, little is known about the biology of this cytokine in BM. In the present study we investigated Th17-related cytokines in RA BM.MethodsBM samples were obtained from RA and osteoarthritis (OA) patients during total hip replacement surgery. Levels of IL-17AF, IL-17AA, IL-17FF, IL-1β, IL-6, IL-23, TGF-β and CCL20 in BM plasma were determined by specific enzyme-linked immunosorbent assay tests. Percentage of IL-17-producing cells in BM was evaluated by flow cytometry. The effect of IL-15 stimulation on IL-17 production by BM mononuclear cells was examined in vitro.ResultsIncreased levels of IL-17AF were observed in BM plasma of RA patients in comparison to OA patients. Increased concentrations of IL-1β, IL-6 and CCL20 were observed in RA compared to OA BM plasma. Concordant with these findings, significantly increased percentages of CD3+CD4+IL-17+ and CD3+CD4+IL-17+IFN-γ+ cells were present in RA BM in comparison to OA BM samples. Finally, abundant in RA BM, IL-15 increased IL-17 production by cultured BM mononuclear cells.ConclusionsIn the course of RA, the BM microenvironment can promote the development of Th17 cell responses and overproduction of IL-17AF that may lead to increased inflammation and tissue destruction in RA BM.
Highlights
Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and disability
IL-17-positive cells are present in Bone marrow (BM) of RA patients Immunohistopathological examination showed the presence of IL-17A-positive cells in BM samples obtained both from RA and OA patients (Fig. 1a–f )
BM bone marrow, IL interleukin, OA osteoarthritis, PB peripheral blood, RA rheumatoid arthritis concentration of IL-17AF heterodimer was higher in BM plasma than in peripheral blood plasma
Summary
Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from “outside the joint” can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and disability [1]. Data obtained in the last decade indicate that bone marrow (BM) is an important compartment in RA, where pathological processes from “outside the joint” can occur. It is assumed that this cytokine overproduction plays a crucial role in inflammation and the development of several autoimmune diseases, including RA. Little is known about biology of this cytokine in BM.
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