Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

BACKGROUND AND AIMS: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). METHODS: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. RESULTS: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. CONCLUSIONS: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

Interleukin-27 and interleukin-37 are elevated in sickle cell anemia patients and inhibit in vitro secretion of interleukin-8 in neutrophils and monocytes.

BACKGROUND AND OBJECTIVE: Inflammation is implicated in the pathogenesis of most complications seen in sickle cell anemia (SCA) patients. We aimed to evaluate serum levels of two newly discovered anti-inflammatory cytokines (IL-27 and IL-37), and pro-inflammatory cytokines among Brazilian SCA patients that are not on hydroxyurea therapy (HbSS), compared with hydroxyurea-treated patients (HbSSHU) and healthy controls (HbAA). Furthermore, we demonstrated the effect of IL-27, IL-37, and heme on in vitro secretions of IL-8 in human neutrophils and monocytes. METHODS: A cross-sectional study of 82 consenting SCA (35 HbSS and 47 HbSSHU) patients in steady state and 49 HbAA consenting individuals. Clinical details were obtained from interviews and medical records. Serum levels of IL-27, IL-37, TGF-ß, TNF-α, IL-1ß, IL-6, and IL-8 were quantified by enzyme linked immunosorbent assay (ELISA). Neutrophils and monocytes were isolated from healthy controls, and cultured separately with or without cytokines (IL-27 and IL-37) and heme. Supernatant IL-8 concentration was determined by ELISA. RESULTS: Serum levels of IL-27, IL-37, IL-1ß, IL-6, and IL-8 were significantly elevated in HbSS patients compared to HbAA controls. Serum IL-8 levels were significantly higher in HbSS and HbSSHU patients than in controls. IL-27 and IL-37 were positively correlated in both HbSS and HbSSHU patients. In vitro IL-8 production by IL-27 and IL-37 pre-treated neutrophils and monocytes was significantly inhibited even after heme addition. CONCLUSIONS: Our findings show that IL-27 and IL-37, as well as the pro-inflammatory cytokines, are elevated in HbSS patients compared with controls, suggesting that the secretion of these anti-inflammatory cytokines is driven by the presence of pro-inflammatory cytokines. This role is probably sufficient in preventing further cellular or tissue damage but not potent enough to prevent inflammation. Therefore, IL-27 and IL-37 may be potential immuno-targets for ameliorating complications associated with elevated heme levels seen in SCA and other hemolytic anemias.