BMDMs Phagocytosis Necrotic hepatocytes Proinflammatory cytokines Crosstalk with innate immune system AAMs Infiltrating neutrophils +IL-4 +IL-13 Endothelial cell proliferation Growth factors Central vein Highlights Primary BMDMs localised to liver and spleen within hours following intravenous injection in mice. AAMs were highly phagocytic and i.v. transfer elicited reductions in necrotic area, HMGB1 translocation, and hepatic neutrophil infiltration. AAM injection reduced inflammatory mediators and stimulated hepatocyte/endothelium proliferation in injured liver. Injection of clinical-grade human AAMs could partially recapitulate the efficacy of murine AAMs in immunocompetent mice.
IntroductionVitamin D deficiency, as assessed by serum concentrations of 25 hydroxyvitamin D (25(OH)D), has been linked to the development of over-zealous and inappropriate inflammation in humans. However, the relationship between vitamin D status and inflammation in dogs is ill-defined. Chronic enteropathies (CE) are frequently diagnosed in client owned dogs, have a wide range of serum 25(OH)D concentrations, and represent a spontaneous model in which to probe the relationship between vitamin D and inflammation. The hypothesis of this study was that vitamin D status would be negatively associated with systemic and gastrointestinal inflammation in dogs with a CE. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and markers of systemic and gastrointestinal inflammation in a cohort of dogs with CE.Methods and MaterialsSerum 25(OH)D concentrations, together with neutrophil, monocyte, eosinophil and lymphocyte counts, duodenal histopathology scores, serum IL-2, IL-6, IL-8 and TNFα concentrations and were measured in 39 dogs with histologically confirmed CE. A linear regression model examined the relationship between serum 25(OH)D status and measures of inflammation.ResultsSerum 25(OH)D concentrations were negatively associated with neutrophil and monocyte counts, duodenal histopathology scores and serum IL-2 and IL-8 concentrations. Dogs with low serum 25(OH)D concentrations typically had an inflammatory signature characterised by high monocyte and neutrophil numbers together with low lymphocyte numbers. There is a need to establish whether low vitamin D status is a cause or consequence of inflammation.
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