The impact of diabetes on the pathogenesis of sepsis

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones

Influence of acute renal failure on the mononuclear phagocytic system

Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung) of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g) were divided into three groups (N = 5): group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05). Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05). Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98) and lung (2.63), and a higher level in the liver (105.51) than control. Group III animals showed a lower level of radioactivity in the spleen (11.94) and a higher level in the liver (61.80), lung (11.30) and blood clot (5.13) than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system

Iron Sucrose Impairs Phagocytic Function and Promotes Apoptosis in Polymorphonuclear Leukocytes

BACKGROUND: With the recent implementation of bundling reimbursement policy the use of intravenous (IV) iron preparations for the management of anemia in the ESRD population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of PMNs against Escherichia Coli. These preparations consist of an elemental iron core and a carbohydrate shell. In addition to the iron core the carbohydrate shell may affect PMNs. We therefore examined the effect of iron sucrose, a commonly used preparation, on phagocytic capacity of PMNs from a group of normal individuals against Gram positive (Staphylococcus Aureus) and Gram negative (E. Coli) bacteria. METHODS: Iron sucrose was added to heparinized blood samples at pharmacologically-relevant concentrations and incubated for 4 and 24 hours at 37° C to simulate in vivo condition. Blood samples mixed with equal volume of saline solution served as controls. To isolate the effects of the carbohydrate shell, blood samples were co-treated with the iron chelator, desferrioxamine. RESULTS: Iron sucrose caused significant PMN apoptosis and dose-dependent suppression of phagocytic function against both Gram positive and negative bacteria. These abnormalities were prevented by desferrioxamine which precluded contribution of the carbohydrate shell to the PMN dysfunction. CONCLUSIONS: At pharmacologically-relevant concentrations iron sucrose promotes apoptosis and inhibits phagocytic activities of PMNs. The deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell, and as such may be shared by other IV iron preparations