Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS).
Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.
Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.
Stefano
S
Caserta
Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.
Florian
F
Kern
Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.
Jonathan
J
Cohen
Brighton and Sussex University Hospitals NHS Trust, Eastern Road, Brighton, BN2 5BE, United Kingdom.
Stephen
S
Drage
Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.
Sarah F
SF
Newbury
Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.|Brighton and Sussex University Hospitals NHS Trust, Eastern Road, Brighton, BN2 5BE, United Kingdom.
Martin J
MJ
Llewelyn
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000737:chemistry; D008875:Middle Aged; D025341:Principal Component Analysis; D012372:ROC Curve; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D035683:MicroRNAs; D002097:C-Reactive Protein