Impaired phagocytic activity of neutrophils in patients receiving haemodialysis: the critical role of iron overload.

Abstract

The metabolic burst (as measured by the spontaneous and stimulated nitroblue tetrazolium tests), the phagocytosis of heat inactivated bakers' yeast and of Staphylococcus aureus, the killing of Staph aureus, and the myeloperoxidase activity of polymorphonuclear neutrophils were studied in 11 patients receiving maintenance haemodialysis. Of these patients, six were polytransfused and had high serum ferritin concentrations (mean 5940 (SD 2925) [tg/l; group 1), and five had normal serum ferritin values (mean 171 (116) [tg/l; group 2). Patients in group 1 had a history of more infectious episodes (0.167 v 0-025 per patient per month) and significantly more genitourinary infections (p=0.015) than those in group 2. Phagocytosis and myeloperoxidase activity were severely reduced in group 1 but normal in group 2. Percentages of neutrophils ingesting one or more particles together with the index of phagocytosis in patients' serum were inversely correlated with serum ferritin concentrations. Four patients in group 1 were treated with desferrioxamine, and after six to 18 weeks of treatment phagocytosis and myeloperoxidase activity had returned to normal in three of them.These data suggest that in patients receiving haemodialysis iron overload due to multiple transfusions plays an important part in the mechanisms underlying the susceptibility to bacterial

Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies.

“…Human polymorphonuclear granulocytes (PMNs) were harvested and purified as previously reported (23). In order to study the effect of PMNs on spore germination, spores were washed in HBSS and incubated in 10% normal human pooled serum during 10 min at 370C, washed in HBSS and diluted to 1,000/Ml.…”

The Fascinating but Deceptive Ferritin

“…There are several reasons for this so-called "iron apprehension": (i) A clinical trial that was performed almost three decades ago in 137 Fe-deficient individuals in Somalia showed that the risk for infection in those who received Fe supplementation was almost five times higher than those who received placebo (63); (ii) in the pre-ESA era, there have been frequent reports about the risk and consequences of Fe overload as a result of blood transfusion or Fe administration to anemic dialysis patients (64,65); (iii) several in vitro studies have indicated the association between Fe supplementation and oxidative stress in cell cultures (66,67); and (iv) a limited number of observational studies have indicated an association between high serum ferritin and infection (65,68) or mortality (52) and between Fe administration and indices of cardiovascular disease (69) or death risk (70) in dialysis patients.…”

Uremia and Infection: Mechanisms of Impaired Cellular Host Defense

“…Another main cause for increased susceptibility to infections in patients with iron load are abnormalities of PM N function [18,24], Waterlot et al [25] described an inverse correlation between ferritin content and index of PMN yeast phagocytosis in hemodial ysis patients. Tielemans et al [26] and Tielemans and Lenclud [27] found increased bacterial infections and septicemia in hemodialysis patients with ferritin levels above 500 pgl/I.…”