Early diagnosis using canonical discriminant analysis of innate immune receptor gene expression profiles in a murine infectious or sterile systemic inflammation model

AbstractBACKGROUNDInfection in patients with systemic inflammation is difficult to diagnose with a single biomarker. We aimed to clarify the time course of change in the gene expression profile of innate immune receptors in infectious or sterile inflammation and to establish an early diagnostic method using canonical discriminant analysis (CDA) of the gene expression profile.METHODSTo compare infectious and sterile inflammation, we used cecal ligation and puncture (CLP) and 20% full-thickness burn injury (Burn) models. C57BL/6 mice underwent sham treatment (n=9×3 groups), CLP (n=12×3 groups), or Burn (n=12×3 groups) injury. Mice were sacrificed at 6, 12, and 24 hours after injury, and total RNA was extracted from whole blood. We used quantitative real-time PCR to investigate gene expression of innate immune receptors TLR2, TLR4, TLR9, NLRP3, and RIG-I. To evaluate all gene expression together as patterns, each value was standardized, and CDA was performed at each time point.RESULTSGene expression of TLR2 and TLR4 was already significantly increased in both CLP and Burn compared to sham mice at 6 hours after injury (p

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