IMMUNOMETABOLISM OF CIRCULATING LEUKOCYTES IN PATIENTS WITH INFECTION AND SEPSIS

herwanto, Velma (2020) IMMUNOMETABOLISM OF CIRCULATING LEUKOCYTES IN PATIENTS WITH INFECTION AND SEPSIS. Doctoral thesis, Universitas Tarumanagara.

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Abstract

Immune dysfunction is a major complication of sepsis. It increases susceptibility to nosocomial infection and contributes significantly to sepsis mortality. Immune dysfunction in sepsis has been associated with alterations in cellular metabolism which manifest as mitochondrial dysfunction and reduced cellular energy production. However, those alterations have been shown in established sepsis patients. Data are lacking in patients who are at early phase of infection who are yet to progress to sepsis. Our study aims to address this knowledge gap. Here, we present findings of a study that investigates metabolic alterations in the immune cells of infection patients. In particular, we compare the findings between those who develop sepsis with findings in those who did not develop sepsis (uncomplicated infection patients) to identify key pathologic mechanisms that underlie the progression from uncomplicated infection towards complicated infection (that is, sepsis). First, in an in vitro model of sepsis, our preliminary experiment on peripheral blood mononuclear cells (PBMCs) indicated reduced mitochondrial respiration with increased intramitochondrial oxidative stress. Second, impaired mitochondrial respiration, with increased intramitochondrial oxidative stress, was observed in the PBMCs of patients with sepsis recruited from the emergency department. The level of oxidative stress significantly correlated with the severity of mitochondrial respiration impairment. Third, the findings of impaired mitochondrial respiration and increased intramitochondrial oxidative stress were also observed in patients with uncomplicated infection, albeit to a lesser intensity. Lastly, xxiii further study on the PBMCs subsets, monocyte and T lymphocytes, corroborated the findings of metabolic alterations in sepsis as well as in uncomplicated infection patients. Altogether, our study found that impaired mitochondrial respiration is detected in the immune cells of patients with uncomplicated infection, as it is in sepsis. Intramitochondrial oxidative stress is among several factors inducing the mitochondrial impairment, raising a possibility of its role as a potential target for preventing immune dysfunction.

Item Type:	Thesis (Doctoral)
Subjects:	Disertasi
Divisions:	Fakultas Kedokteran > Kedokteran
Depositing User:	Erik Wijaya
Date Deposited:	31 Jan 2022 07:41
Last Modified:	31 Jan 2022 07:41
URI:	http://repository.untar.ac.id/id/eprint/33814

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