AIM/HYPOTHESIS: Monocytes/macrophages play important roles in adipose and vascular tissues and can be polarised as inflammatory M1 or anti-inflammatory M2. We sought to analyse monocyte polarisation status in type 2 diabetes, which is characterised by chronic inflammation. METH-ODS: We enrolled 60 individuals without diabetes and 53 patients with type 2 diabetes. We quantified standard monocyte subsets defined by cluster of differentiation (CD)14 and CD16. In addition, based on the phenotype of polarised macrophages in vitro, we characterised and quantified more definite M1 (CD68(+)CCR2(+)) and M2 (CX3CR1(+)CD206(+)/CD163(+)) monocytes. We also analysed bone marrow (BM) samples and the effects of granulocyte-colony stimulating factor (G-CSF) stimulation in diabetic and control individuals. RESULTS: We found no alterations in standard monocyte subsets (classical, intermediate and non-classical) when comparing groups. For validation of M1 and M2 phenotypes, we observed that M2 were enriched in non-classical monocytes and had lower TNF-content, higher LDL scavenging and lower transendothelial migratory capacity than M1. Diabetic patients displayed an imbalanced M1/M2 ratio compared with the control group, attributable to a reduction in M2. The M1/M2 ratio was directly correlated with waist circumference and HbA1c and, among diabetic patients, M2 reduction and M1/M2 increase were associated with microangiopathy. A decrease in M2 was also found in the BM from diabetic patients, with a relative M2 excess compared with the bloodstream. BM stimulation with G-CSF mobilised M2 macrophages in diabetic but not in healthy individuals. CON-CLUSIONS/INTERPRETATION: We show that type 2 diabetes markedly reduces anti-inflammatory M2 monocytes through a dysregulation in bone-marrow function. This defect may have a negative impact on microangiopathy. DOI: https://doi.org/10.1007/s00125-013-2918-9Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-83908 Accepted Version Originally published at: Fadini, G P; de Kreutzenberg, S Vigili; Boscaro, E; Albiero, M; Cappellari, R; Kränkel, N; Landmesser, U; Toniolo, A; Bolego, C; Cignarella, A; Seeger, F; Dimmeler, S; Zeiher, A; Agostini, C; Avogaro, A (2013). An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy. Diabetologia, 56 (8) (CX3CR1+CD206+/CD163+) monocytes. We also analysed bone marrow (BM) samples and the effects of G-CSF stimulation in type 2 diabetic and control subjects.Results. We found no alterations in standard monocyte subsets (classical, intermediate, and nonclassical) between groups. For validation of M1 and M2 phenotypes, we show that M2 were enriched in nonclassical monocytes, had lower TNF-α content, higher LDL scavenging and lower transendothelial migratory capacity than M1. Diabetic patients displayed an imbalanced M1/M2 ratio compared to controls, which was attributable to a reduction in M2. The M1/M2 ratio was d...

Estrogen treatment prevented LPS/IFN-γ action on human M2 macrophage markers and cytokine production, whereas menopausal estrogen loss was associated with an impaired response to alternative activation, suggesting that these mechanisms affect the cardiovascular risk profile in relation to menopausal status.

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Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food.

In this study, four prenylated and geranylated flavonoids, cudraflavone B (1), pomiferin (2), osajin (3), and diplacone (4), were tested for their antioxidant and anti-inflammatory effects and to identify any potential relationships between chemical structure and antioxidant or anti-inflammatory properties. The selected flavonoids were examined in cell-free models to prove their ability to scavenge superoxide radicals, hydrogen peroxide, and hypochlorous acid. Further, the ability of the flavonoids to influence the formation of reactive oxygen species in the murine macrophage cell line J774.A1 was tested in the presence and absence of lipopolysaccharide (LPS). The ability of flavonoids to inhibit LPS-induced IκB-α degradation and COX-2 expression was used as a model for the inflammatory response. The present results indicated that the antioxidant activity was dependent on the chemical structure, where the catechol moiety is especially crucial for this effect. The most potent antioxidant activities in cell-free models were observed for diplacone (4), whereas cudraflavone B (1) and osajin (3) showed a pro-oxidant effect in J774.A1 cells. All flavonoids tested were able to inhibit IκB-α degradation, but only diplacone (4) also down-regulated COX-2 expression.