ANEMIA OF INFLAMMATION: INVESTIGATION ON HEPCIDIN IN ACUTELY ILL PATIENTS AND THEIR CLINICAL OUTCOME
Creators: name: CARRABBA, MARIA DOMENICA ROSARIA
Publisher: name: Universit� degli Studi di Milano
Year: 2013

description: The anaemia of inflammation is a normochromic, normocytic anaemia, associated with abnormal iron utilization, erythropoietin hyporesponsiveness, and decreased red blood cells (RBC) survival. It is a very common problem in hospitalized patients for acute inflammatory diseases and develops within few days from the onset of illness. Hepcidin is an interleukin-6 induced hormone previously identified as an antimicrobial peptide. Now it is recognized as the master regulator of iron homeostasis in mammals allowing iron adaptation according to the body iron needs and as the key modulator of inflammation-associated anaemia. Hepcidin is found in the circulation, it is secreted mainly by hepatocytes and to a lesser extent by macrophages, T-lymphocytes and adipocytes. In 60 acutely ill patients (95% affected by infections), the degree of inflammation, indicated by IL-6 and C-RP levels, is associated with elevated concentrations of hepcidin, low iron serum levels, high transferrin saturation and very high ferritin serum levels. Moreover, persistently increased levels of hepcidin-25 on T1 and on T6 are associated with a decrease in haemoglobin during hospitalization. Patients (N=26) anaemic on T1 were still anaemic after one week. Erythropoiesis was still blunted in these patients, despite higher erythropoietin serum levels than notanaemic patients. The high levels of GDF-15 and hepcidin could have a role in the ineffective erythropoiesis. We observed that acute ill patients (N=31) admitted with normal haemoglobin levels develop anaemia after the first week of hospitalization. Analysing hepcidin levels of this subset of patients, we found that a cut-off level of hepcidin concentration of 23 nM/L was able to predict anaemia occurrence after one week with 100% of sensitivity and 90% of specificity. The inflammatory cytokines pattern and its consequence on hepcidin and iron observed in vivo in this study resembles the one described in experimental models of endotoxemia showed by Kemna et al. and by Theurl et al. Also hepcidin serum levels, haemoglobin and iron parameters are very similar to the ones found by van Eijk et al. in their investigation in septic patients admitted to intensive care units. As described in previous studies, we also demonstrated expression of hepcidin mRNA in circulating monocytes of these acutely ill patients. We found that the higher was the inflammation on admission, the higher was hepcidin mRNA expression in circulating monocytes after one week. Moreover we found negative correlation between mRNA levels of monocytes-derived hepcidin and serum ferritin, especially after one week of inflammation persistence. Analysis of interleukin-6 functional receptor (CD126 and gp130) on circulating monocytes showed a negative correlation with monocytes-derived hepcidin mRNA, and positive correlation with serum ferritin levels. These insights in anaemia of inflammation molecular mechanisms will help clinicians to better identify anaemia causes and adequately restore haemoglobin concentration with target therapies, reducing health-care requirements and healthcare costs, in-hospital stay and, finally, ameliorate health of patients.