Articular adipose tissue resident macrophages in rheumatoid arthritis patients: potential contribution to local abnormalities

Objectives. The objectives of this study were to characterize macrophages resident in inflamed articular adipose tissue (AAT) and non-inflamed subcutaneous adipose tissue (ScAT) of RA patients and to evaluate the basal and cytokine-triggered secretory activities of these tissues. Methods. Tissues were obtained from patients undergoing knee joint replacement surgery. The number of total CD68(+), CD14(+) and CD163(+) macrophages was evaluated by immunohistochemistry. The concentrations of select factors were measured in supernatants from untreated and cytokine-treated tissue explant cultures using ELISA. IL-1 beta and TNF were applied as the stimuli. Results. Paired samples of AAT and ScAT, obtained from the same patients, contained a similar number of macrophages, displaying an M2-skewed phenotype. Both tissues released equivalent amounts of IL-1 beta, TNF, IL-10 and macrophage migration inhibitory factor (MIF). However, AAT secreted more chemokines (CCL2, CCL5), cytokines [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra)], hepatocyte growth factor (HGF) and MMP-3 than ScAT. Basal secretion of adipocytokines was not patient specific. Except for HGF and MIF, cytokine treatment up-regulated the release of these factors from both tissues, but also upon stimulation AAT produced more IL-6, IL-8 and IL-1Ra than ScAT. Conclusion. The secretory activity, reflecting cell activation status but not phenotype or the number of macrophages, discriminates rheumatoid AAT from ScAT. By releasing various factors possessing chemotactic, proinflammatory, anti-inflammatory and tissue degrading activities, AAT resident macrophages may drive and control local pathological processes.