- Oral presentation
- Open Access
Long-Term Follow-Up of Sepsis Induced Immunoparalysis
© Raja et al.; 2015
- Published: 1 October 2015
- Consecutive Adult Patient
- Follow Hospital Discharge
- Grant Acknowledgment
- Express Cell Surface
- Bacteraemic Patient
Severe sepsis induces a state of immunoparalysis. Animal models have demonstrated this to be secondary to microbial-induced host epigenetic alterations, which persist and are associated with long-term immunoparalysis. Whilst human sepsis is associated with poor long-term outcomes in conjunction with recurrent infections, it is not clear if the immunoparalysed state persists following recovery from the initial septic insult.
1. To confirm the presence of circulating mediators capable of causing immunoparalysis following bacteraemia.
2. To assess for the presence of immunosuppressive mediators following hospital discharge with full functional recovery.
Consecutive adult patients (n = 7) with bacteraemia and an admission diagnosis of infection were recruited. Serum was collected at 3 time points; within 48 hours of the positive blood culture, 5 days later & 12 months following hospital discharge. Peripheral blood mononuclear cells (PBMCs) were collected from a healthy control cohort (n = 7) and pooled. Healthy PBMCs were co-cultured with 30% septic serum for 20 hours with and without GM-CSF (200ng/ml). CD14+HLA-DR (mHLA-DR) geometric-mean fluorescent intensity (MFI) was determined using flow cytometry. Data were analysed with non-parametric statistics with results presented as median & IQR .
Circulating mediators present in the serum of bacteraemic patients reduces the ability of healthy monocytes to express cell surface HLA-DR, which is reversible in the presence of an immunostimulant. Serum from patients following full recovery from the acute illness does not reduce HLA-DR expression on healthy monocytes.
ESICM Basic Science Award 2014.
- Deng JC, et al: Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest. 2006, 116: 2532-42.PubMedPubMed CentralGoogle Scholar
- Carson WF, et al: Epigenetic regulation of immune cell functions during post-septic immunosuppression. Epigenetics. 2011, 6: 273-83. 10.4161/epi.6.3.14017.PubMedPubMed CentralView ArticleGoogle Scholar
- Czaja AS, et al: Readmission and late mortality after paediatric severe sepsis. Paediatrics. 2009, 123: 849-10.1542/peds.2008-0856.View ArticleGoogle Scholar
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