Abstract
BackgroundSeasonal influenza is an important cause of morbidity and mortality worldwide. Immune activation after stimulation with interferon‐gamma leads to increased production of neopterin but also results in increased tryptophan catabolism through indoleamine 2,3‐dioxygenase (IDO). Our pilot study determined neopterin serum levels and IDO activity in patients with influenza infection and investigated whether neopterin is linked to clinical outcome parameters (mortality ≤30 days, acute cardiac events (ACE) length of hospitalization, ICU admission).MethodsNeopterin concentrations were analyzed in serum samples of 40 patients with a confirmed diagnosis of influenza infection and in‐hospital treatment for >24 hours. Data were compared to values of 100 healthy blood donors and 48 age‐matched pneumonia patients. In a subgroup of 14 patients, tryptophan and kynurenine concentrations, as well as kynurenine‐to‐tryptophan ratio, were analyzed.ResultsIn all influenza patients, neopterin concentrations were increased and significantly higher compared to those determined in patients with pneumonia and healthy controls. Positive correlations between the duration of hospitalization and neopterin were found. Significantly higher levels of kynurenine, kynurenine‐to‐tryptophan ratio, and lower levels of tryptophan were seen in influenza patients compared to healthy controls.ConclusionsNeopterin seems to be related to the course of the disease and could be a valuable biomarker to identify patients at an elevated risk of a worsened outcome; however, further prospective validation studies are needed to support the here presented preliminary results.
Highlights
Seasonal influenza is an important cause of morbidity and mortal‐ ity worldwide, with an annual incidence rate estimated between 5% and 10% in adults and 20% and 30% in children, resulting in about 290 000‐650 000 deaths per year.[1]
We found significantly higher levels of neopterin (P < .01), kynurenine (P < .01), kynurenine‐to‐tryptophan ratio (Kyn/Trp) (P < .01), and lower levels of tryptophan (P < .01) when comparing influenza patients to healthy controls (Figures 2 and 3)
We were able to show an elevation of neopterin serum levels at the diagnosis of influenza infection
Summary
Seasonal influenza is an important cause of morbidity and mortal‐ ity worldwide, with an annual incidence rate estimated between 5% and 10% in adults and 20% and 30% in children, resulting in about 290 000‐650 000 deaths per year.[1]. Since influenza antigen bed‐side tests have limited sensitivity and polymerase chain reaction (PCR)‐based methods are expensive and often not available, cheaper and more reliable biomarkers for diagnosis, and risk stratification of patients with influenza infection are desired.[20] The aim of this pilot study was to investigate neopterin levels and IDO activity in sera of hospitalized patients with influenza infection and to analyze correlations with clinical outcome parameters in a small real‐life cohort. Tryptophan and kynurenine concen‐ trations were measured by high‐performance liquid chromatog‐ raphy (HPLC) on reversed phase, and the ratio of kynurenine to tryptophan (Kyn/Trp) was calculated to estimate IDO activity.[21] Neopterin concentrations were determined by ELISA (BRAHMS Diagnostica) These results were compared to a historical cohort of 100 healthy volunteers.[22] The healthy volunteers were recruited from the Central Institute of Blood Transfusion and Immunology of the University Clinics Innsbruck after exclusion of infection or active diseases. Statistical analyses were performed with the SPSS 24.0 statistical package (IBM Corp.)
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