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Sepsis represents a systemic illness, characterized by life-threatening organ dysfunction induced by infection. Early diagnostic, evaluation of severity of sepsis with aggressive resuscitation and administration of appropriate antibiotics are associated with improved outcomes. In 2016 a new definition of sepsis (Sepsis-3) was proposed. The key element of sepsis-induced organ dysfunction is defined by "an acute change in total SOFA score >= 2 points consequent to infection". The use of SIRS criteria as identification of sepsis was abandoned and subcategory of severe sepsis was eliminated. A wide spectrum of biomarkers had been proposed for potential use in sepsis, more than in other diseases, outlying the complex pathophysiology of this condition. The first study reporting the clinical value of circulating miRNAs in sepsis showed that both leukocytes and plasma miR-150 levels are significantly reduced in sepsis patients compared with controls and correlate with sepsis severity. Several miRNAs were found differentially expressed in sepsis patients, but most of the published studies failed to find miRNA biomarkers that could differentiate sepsis from SIRS. A solution to this problem seems to be building and analyzing miRNA network in sepsis patients., (Celsius.)

Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities. Biomarkers are potentially valuable clinical tools in this context, but to date, no single biomarker has been shown to perform adequately. Hence, in an effort to discover novel diagnostic and prognostic markers in sepsis, new genomic approaches have been employed. As a result, a number of small regulatory molecules called microRNAs (miRNAs) have been identified as key regulators of the inflammatory response. Although deregulated miRNA expression is increasingly well described, the pathophysiological roles of these molecules in sepsis have yet to be fully defined. Moreover, non-human miRNAs, including two Kaposi Sarcoma herpesvirus-encoded miRNAs, are implicated in sepsis and may drive enhanced secretion of pro-inflammatory and anti-inflammatory cytokines exacerbating sepsis. A better understanding of the mechanism of action of both cellular and viral miRNAs, and their interactions with immune and inflammatory cascades, may therefore identify novel therapeutic targets in sepsis and make biomarker-guided therapy a realistic prospect.

Background: The physiopathology of sepsis continues to be poorly understood, and despite recent advances in its management, sepsis is still a life-threatening condition with a poor outcome. If new diagnostic markers related to sepsis pathogenesis will be identified, new specific therapies might be developed and mortality reduced. Small regulatory non-coding RNAs, microRNAs (miRNAs), were recently linked to various diseases; the aim of our prospective study was to identify miRNAs that can differentiate patients with early-stage sepsis from healthy controls and to determine if miRNA levels correlate with the severity assessed by the Sequential Organ Failure Assessment (SOFA) score., Methodology/principal Findings: By using genome-wide miRNA profiling by microarray in peripheral blood leukocytes, we found that miR-150, miR-182, miR-342-5p, and miR-486 expression profiles differentiated sepsis patients from healthy controls. We also proved by quantitative reverse transcription-polymerase chain reaction that miR-150 levels were significantly reduced in plasma samples of sepsis patients and correlated with the level of disease severity measured by the SOFA score, but were independent of the white blood counts (WBC). We found that plasma levels of tumor necrosis factor alpha, interleukin-10, and interleukin-18, all genes with sequence complementarity to miR-150, were negatively correlated with the plasma levels of this miRNA. Furthermore, we identified that the plasma levels ratio for miR-150/interleukin-18 can be used for assessing the severity of the sepsis., Conclusions/significance: We propose that miR-150 levels in both leukocytes and plasma correlate with the aggressiveness of sepsis and can be used as a marker of early sepsis. Furthermore, we envision miR-150 restoration as a future therapeutic option in sepsis patients.

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non‐infectious complications, with unknown mechanisms. In order to explore the role of the non‐coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR‐223 was overexpressed immediately and late after splenectomy, while miR‐146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR‐16, miR‐93, miR‐26a and miR‐26b were overexpressed only late after splenectomy, suggesting similarities with sepsis. We also explored the non‐coding (nc)RNome of circulating peripheral blood leucocytes by performing a ncRNA full genome profiling. We observed a reorganization of the ncRNoma after splenectomy, characterized by up‐regulation of miRNAs and down‐regulation of transcribed pyknons (T‐PYKs). Pathway analysis revealed that deregulated miRNAs control pathways involved in immunity, cancer and endothelial growth. We checked the expression of the ncRNAs in 15 immune cell types from healthy donors and observed that plasma miRNAs, cellular miRNAs and T‐PYKs have a cell‐specific expression pattern and are abundant in different types of immune cells. These findings suggest that the ncRNAs potentially regulate the immune changes observed after splenectomy. [ABSTRACT FROM AUTHOR]