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IL-1/tumor necrosis factor receptor gene expression characterizes sepsis in critically ill systemic inflammatory response syndrome patients

Introduction

The classic response to isolated endotoxin challenge entails secretion of IL-1 and TNFα . The purpose of this study was to longitudinally characterize the cytokine response to sepsis in critically ill systemic inflammatory response syndrome (SIRS) patients.

Methods

Uninfected, critically ill trauma patients with SIRS were evaluated daily for sepsis. Patients were divided into two groups: pre-septic = SIRS patients who developed sepsis, and uninfected SIRS = SIRS patients remaining uninfected. Plasma samples and whole blood (PAXgene) obtained at study entry and daily for 3 days prior to sepsis were analyzed for differential gene expression between groups (Affymetrix Hg_U133 2.0 plus microarray, false discovery rate < 0.5%, P < 0.005) and quantitative plasma protein TNF and IL-1 levels (Immunoassay, Luminex™, elevated if > 3 SD above the mean for normals). Gene expression data are the median fold change between groups (uP = pre-septic > uninfected).

Results

Gene expression on 90 patients and protein measurements on 142 patients were available. Protein levels of both subtypes of TNF and IL-1 were not elevated at any time point in either group. IL-1α was noted to have differential gene expression 24 hours before sepsis. No differences were noted in gene expression for TNFα, TNFβ, or IL-1β . Differential gene expression for only two TNF family members (TNFSF10 and TNFSF13b) was noted. However, differential gene expression for TNF and IL-1 receptors and IL-1 receptor antagonist was prominent (Table 1).

Table 1 (abstract P449)

Conclusion

Compared with critically ill uninfected SIRS patients, sepsis increases IL-1α but not TNFα gene expression and does not increase TNF and IL-1 protein levels. Interestingly differential gene expression for TNF and IL-1 receptors exists, suggesting receptors, more than ligands, are important in differentiating sepsis from uninfected SIRS.

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Lissauer, M., Johnson, S., Feild, C. et al. IL-1/tumor necrosis factor receptor gene expression characterizes sepsis in critically ill systemic inflammatory response syndrome patients. Crit Care 11, P449 (2007). https://doi.org/10.1186/cc5609

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Keywords

  • Systemic Inflammatory Response Syndrome
  • Differential Gene Expression
  • Tumor Necrosis Factor Receptor
  • Receptor Gene Expression
  • Classic Response