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OBJECTIVE: Mitochondrial dysfunction, linked to sepsis-related organ failure, is unknown in febrile illness. METHODS: Prospective study of children in an Emergency Department (ED) with febrile illness or without infection (ED controls); secondary analysis of ICU patients with sepsis or without infection (ICU controls). Mitochondrial oxygen consumption measured in peripheral blood mononuclear cells using respirometry, with primary outcome of spare respiratory capacity (SRC). Mitochondrial content measured as citrate synthase (CS: febrile illness and ED controls) and mitochondrial to nuclear DNA ratio (mtDNA:nDNA: all groups). RESULTS: SRC was lower in febrile illness (6.7 ± 3.0 pmol/sec/106 cells) and sepsis (5.7 ± 4.7) than ED/PICU controls (8.5 ± 3.7; both p < 0.05), but not different between febrile illness and sepsis (p = 0.26). Low SRC was driven by increased basal respiration in febrile illness and decreased maximal uncoupled respiration in sepsis. Differences were no longer significant after adjustment for patient demographics. Febrile illness demonstrated lower CS activity than ED controls (p = 0.07) and lower mtDNA:nDNA than both ED/PICU controls and sepsis (both p < 0.05). CONCLUSION: Mitochondrial SRC was reduced in both febrile illness and sepsis, but due to distinct mitochondrial profiles and impacted by demographics. Further work is needed to determine if mitochondrial profiles could differentiate febrile illness from early sepsis. IMPACT STATEMENT: Mitochondrial dysfunction has been linked to organ failure in sepsis, but whether mitochondrial alterations are evident in febrile illness without sepsis is unknown. In our study, while mitochondrial spare respiratory capacity (SRC), an index of cellular bioenergetic reserve under stress, was reduced in children with both febrile illness and sepsis compared to children without infections, low SRC was driven by increased basal respiration in febrile illness compared with decreased maximal uncoupled respiration in sepsis. Additional research is needed to understand if distinct mitochondrial profiles could be used to differentiate febrile illness from early sepsis in children.
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PROBLEM: Interferon epsilon (IFNε) is a unique type I IFN that is expressed in response to sex steroids. Studies suggest that type I IFNs regulate inflammation-induced preterm birth (PTB), but no study has examined the role of IFNε in human pregnancy. METHOD OF STUDY: We used stored vaginal swabs between 8 and 26 weeks of gestation from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) biobank and measured IFNε by enzyme-linked immunosorbent assay (ELISA). A total of 29 women with spontaneous preterm births, 34 women with medically indicated preterm births, and 134 women with term births were included. Secondary outcomes included a preterm birth with chorioamnionitis and preeclampsia with a preterm birth. Logistic regression calculated odds ratios (OR) and 95% confidence intervals (CI) adjusting for maternal age, race, body mass index, prior pregnancy complications, lower genital tract infections, chronic health conditions, and gestational age at blood draw. RESULTS AND CONCLUSIONS: There was no significant association between IFNε and spontaneous preterm birth (ORadj 1.0, 0.8-1.3) or chorioamnionitis (ORadj 1.6, 0.7-3.5). A trend toward increased odds of medically indicated preterm birth (ORadj . 1.3, 1.0-1.8) was observed. This was likely due to elevated IFNε among women with preterm preeclampsia (ORadj . 2.0, 95% CI 1.3-3.2). While exploratory, our novel findings suggest that larger longitudinal studies of IFNε across human pregnancy may be warranted.