Serum IL-6, IL-10, TNF-α and IFN-γ bio-signature for neonatal sepsis diagnosis and treatment outcome

Diagnosing sepsis in preterm neonates is a significant challenge, underscoring the urgent need for timely and accurate methods. In this study, preterm neonates (n=252, 25 to 35 weeks gestation, female: 40%) from sepsis suspected (n=188) and healthy controls (n=64) were enrolled. Based on the microbiology and mass spectrometry data, the sepsis suspects were categorized into culture-positive/negative (CP/CN) or no sepsis (NS). Serum inflammatory proteins were profiled using the Olink Target 96 inflammation panel and validated in independent sets using ELISA, multiplex cytokine arrays and qRT-PCR. Serum trace elements (Fe, Zn, Cu, Se, Ca, Mg) were profiled using inductively coupled plasma mass spectrometry (ICP-MS). An increased IL-6: IFN-{gamma} ratio was observed in CP and CN, which normalised upon recovery. Elevated serum IL-6, TNF-, and IL-10 levels were observed in the CP sepsis groups with respect to CN. A reduced serum IFN-{gamma} level was observed in the CP, CN and NS groups. The qRT-PCR of IL6, TNFA, and IL10 showed higher expression in the Cd45+ leukocytes of CP and CN compared to the HC groups, which decreased upon recovery. Serum iron levels were significantly lower in the CP group, indicating anaemia of inflammation, which normalised upon completion of the therapeutic regimen. Serum inflammatory proteins showed group-specific trends, and the serum biosignatures of IL-6, IL-10, IFN-{gamma}, and TNF- could be useful for distinguishing sepsis subtypes and for diagnosing and monitoring therapeutic responses in neonatal sepsis.