The Significance of Iron in Infection

Bullen, J. J.

doi:10.1093/clinids/3.6.1127

Cited by 571 publications

(406 citation statements)

References 65 publications

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“…9 Hyperferraemia can predispose to bacterial and fungal infections. 10 Increased TS and ferritin are proven risk factors for the development of systemic fungal infections in patients with haematological malignancies, 11 and, accordingly, patients submitted to liver transplant caused by haemo-chromatosis are at a greater risk of dying from fungal infections than patients without iron overload submitted to the same transplant type. 12 An increase in some late fungal infections, specially mucormycosis, have been reported in iron loaded patients after HSCT.…”

Section: Discussionmentioning

confidence: 99%

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

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Remacha

Sureda

et al. 2002

Bone Marrow Transplant

116

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Summary:Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (у3000 g/l) and transferrin saturation (TS) у100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days ؊7 and ؊4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS у100% were associated with a decreased OS (P ‫؍‬ 0.001 and P ‫؍‬ 0.006, respectively) and an increased TRM (P ‫؍‬ 0.003 and P ‫؍‬ 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P ‫؍‬ 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P ‫؍‬ 0.01). Ferritin was very close to achieving statistical significance for TRM (P ‫؍‬ 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS у100% at conditioning are associated with an increase in toxic deaths after transplant. Bone Marrow Transplantation (2002) 29, 987-989. DOI: 10.1038/sj/bmt/1703570 Keywords: iron; transferrin saturation; ferritin; survival; TRM; HSCT Iron overload (IO) is associated with free radical production and tissue damage in different diseases such as genetic haemochromatosis and secondary IO. 1,2 IO may be present among patients who undergo haematopoietic stem cell transplantation (HSCT) due to prior blood transfusions. Pre-transplant iron status may be evaluated measuring ferritin levels pre-conditioning; that is a time when ferritin is still neither increased as an acute phase reactant nor influenced by liver toxicity secondary to chemo-radiotherapy. Moreover, transferrin saturation (TS) increases during chemo-radiotherapy, often reaching indexes of over 80% and producing non-transferrin-bound iron (NTBI). 3,4 TS might inform us about the potentially toxic effect of free iron, without any protein control, produced during conditioning. It is likely that an IO status pre-conditioning with an elevated TS during this procedure for HSCT may increase the toxic effects of chemo-radiotherapy. 5 This could cause an increase in transplant-related mortality (TRM) and a subsequent decrease in overall survival (OS). The aim of this study was to determine whether a very high level of ferritin pre-conditioning and/or a full TS during CY-TBI were independent risk factors for TRM and OS. Patients and methodsTwenty-five consecutive patients who underwent HSCT with CY/TBI were prospectively enrolled in the study. All patients were conditioned with cyclophosphamide 60 mg/kg once daily i.v. on days Ϫ6 and Ϫ5 (total dose 120 mg/kg) and TBI 6 ϫ 2 Gy from days Ϫ3 to Ϫ1. GVHD prophylaxis in...

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Section: Discussionmentioning

confidence: 99%

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

Altés

Remacha

Sureda

et al. 2002

Bone Marrow Transplant

116

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“…[3][4] These adverse events and the high availability of free iron might increase microbial growth and the probability of severe infections. 5 Indeed, iron is an essential element for all pathological microorganisms. It is therefore possible that iron overload may significantly increase transplant-related mortality (TRM) due to toxic death and lethal infections in immunocompromised patients.…”

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confidence: 99%

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

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Remacha

Sarda

et al. 2004

Bone Marrow Transplant

119

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Summary:Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n ¼ 24) or allogeneic (n ¼ 35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 lmol/g dry weight (7.7 mg/g; range 31-631 lmol/g). In total, 4/32 (12%) patients with HIC o150 lmol/g and 10/27 (37%) with hepatic iron X150 lmol/g showed invasive aspergillosis at autopsy (P ¼ 0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P ¼ 0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

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“…Zn metalloenzymes are known to participate in many metabolic processes, including carbohydrate metabolism and the synthesis and degradation of lipid, protein, and nucleic acid (Li & Vallee, 1980 competence (Bullen, 1981). Plasma levels of copper, in the form of caeruloplasmin, are elevated by IL-1 (Dinarello, 1984a(Dinarello, ,b, 1988.…”

Section: Znterleukin-i and Tumour Necrosis Factor: The Acute-phase Rementioning

confidence: 99%

“…However, care must be taken when administering Fe to the malnourished patient with inflammation who also has low levels of plasma protein, since increased levels of free Fe in conjunction with low concentrations of serum transferrin can increase susceptibility to bacterial pathogens (Bullen, 1981).…”

Section: )mentioning

confidence: 99%

Nutrition, Immune Function, and Inflammation: an overview

1989

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The account of acute inflammation is one of the classical clinical descriptions in medicine. However, those early physicians describing Rubor et tumor cum calor et dolore (Celsus in 50 BC) could hardly have imagined the complexity of the events that they were observing.In a healthy individual, the response to tissue injury and infection is rapid and efficient, with resolution occurring before involvement of the specific immune system. However, when the inflammatory stimulus is overwhelming, or if the patient is already malnourished or chronically ill, a series of inter-related events are set in motion. Among these are the interaction of immune cells, phagocytes and release of powerful cytokines that affect the utilization of nutritional substrates in the body. Moreover, antigen processed by macrophages is presented to lymphocytes, thus eliciting a specific immune response.The present paper summarizes our present understanding of the pathophysiology of inflammation and explores the objectives for nutritional support in the presence of immunodysfunction. The rationale for adjunctive nutritional support is explained, and modified regimens, tailored both to provide metabolic substrates and to enhance immunity to disease, are given. Pathophysiology of the inflammatory responseThe immune system is phylogenetically separated into innate or non-specific immunity and the adaptive or specific immune system. While understanding that both processes are often working together, events in each system will be considered individually at a cellular and molecular level.Non-specific immunity. Tissue injury leads to release of Hageman factor (XIIa-XII) and to the degranulation of tissue mast cells. Factor XI1 initiates the process, causing complement activation and bradykinin production locally. Micro-organisms and endotoxin may also trigger this pathway, directly activate complement, or cause mast cell degranulation ( Fig. 1) (Schlesinger, 1975). This mechanism ensures the presence of inflammatory mediators such as the complement factors C3a and C5a, bradykinin, and histamine. Damaged cell membranes release products of arachidonic acid (AA) metabolism, such as prostaglandins (PG) and leukotrienes (LT) (Goetzl, 1981), both of which are eicosanoids having important mediating functions in acute inflammation. The net effect is to increase vascular pernieability, which causes the accumulation of acute-phase at https://www.cambridge.org/core/terms. https://doi

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The Significance of Iron in Infection

Cited by 571 publications

References 65 publications

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

Nutrition, Immune Function, and Inflammation: an overview

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