Cross-Regulation of Iron and Glucose Metabolism in Response to Infection

Carlos, Ana Rita; Weis, Sebastian; Soares, Miguel P.

doi:10.1021/acs.biochem.7b00728

Cited by 2 publications

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“…Alterations of iron homeostasis in the setting of sepsis are driven by cytokines and acute phase proteins along with their effects on erythropoiesis and erythrocyte damage. While these subtle alterations are considered as a defense strategy of the body against invading microbes, alterations of iron homeostasis may negatively impact on metabolic processes of cells including mitochondrial respiration, immune function, or tissue oxygen supply [27,28].…”

Section: Discussionmentioning

confidence: 99%

Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study

et al. 2020

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Background Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body’s iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis. Methods Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects. Results Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA–TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients. Conclusions Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score. Trial registration The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).

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Section: Discussionmentioning

confidence: 99%

Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study

et al. 2020

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“…More recently a crosstalk between iron and glucose metabolism has also been established in the context of infections ( 14 , 115 , 116 ). Namely, iron intake from diet leads to decreased pathogen virulence, without interfering with pathogen burden, favoring asymptomatic infection with the enteric pathogen C. rodentium ( 116 ).…”

Section: Cross-talk Between Iron and Glucose Metabolism In Response Tmentioning

confidence: 99%

Cross-Talk Between Iron and Glucose Metabolism in the Establishment of Disease Tolerance

2018

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Infectious diseases are associated with disruption of host homeostasis. This can be triggered directly by pathogens or indirectly by host immune-driven resistance mechanisms. Disease tolerance is a defense strategy against infection that sustains host homeostasis, without exerting a direct negative impact on pathogens. The mechanisms governing disease tolerance encompass host metabolic responses that maintain vital homeostatic parameters within a range compatible with survival. Central to this defense strategy is the host's ability to sense and adapt to variations in nutrients, such as iron and glucose. Here we address how host responses regulating iron and glucose metabolism interact to establish disease tolerance and possibly modulate resistance to infection.

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Cross-Regulation of Iron and Glucose Metabolism in Response to Infection

Cited by 2 publications

References 5 publications

Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study

Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study

Cross-Talk Between Iron and Glucose Metabolism in the Establishment of Disease Tolerance

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