IRON ACCUMULATION AND METABOLIC CHANGES IN MONOCYTES CORRELATE WITH DISEASE SEVERITY IN SEPSIS

Sepsis is a frequent, often lethal syndrome caused by a maladaptive immune and metabolic response to infection. Alterations of iron metabolism play a crucial role in sepsis immunology. Iron markers not only indicate inflammation but reflect upon an active crosstalk with cellular immunity and can indicate prognosis and mortality of critically ill patients. Moreover, severe iron-deficiency at discharge from hospital is an independent predictor of poor physical recovery, making allogenic blood transfusions necessary. As of now, the mechanisms that link iron metabolism and sepsis progression are incompletely understood. We performed an observational study to analyze changes in iron parameters during the course of gut-origin sepsis. Whole blood was drawn daily from day 1 to day 5 after sepsis diagnosis and the patient’s immunological status, systemic iron parameters and the iron content of CD14+ monocytes was quantified by atomic-absorption-spectrometry. We show that systemic iron parameters correlate with the severity of sepsis, in that serum iron and transferrin saturation were significantly lower in severely affected patients compared to those with a mild sepsis. Patient derived monocytes were severely iron-loaded during sepsis progression in a manner that correlated with disease severity and systemic inflammation. Consistently, the mRNA expression of transferrin receptor 1 was decreased. Seahorse analysis investigating the monocytic metabolic state provides indications that monocytic iron loading may alter mitochondrial function pointing towards a strong link between iron metabolism and monocyte function that needs to be elucidated further.