Volume 14 Supplement 1

30th International Symposium on Intensive Care and Emergency Medicine

Open Access

Alterations of caspase 9 mRNA gene expression in survivors and nonsurvivors of severe sepsis

  • M White1,
  • D Doherty2,
  • D Kelleher2,
  • R McManus2 and
  • T Ryan1
Critical Care201014(Suppl 1):P7

https://doi.org/10.1186/cc8239

Published: 1 March 2010

Introduction

Sepsis-induced lymphocyte apoptosis plays a fundamental role in the pathophysiology of sepsis. Recent animal models of sepsis have identified anomalies in the extrinsic apoptotic pathway, a key pathological occurrence in sepsis [1]. Specifically apoptosis markers such as caspases 1, 3, 8, 9 and FADD have been shown to be significant in animal models of infection [2]. We investigated mRNA transcription of these markers in a human model of severe sepsis. We hypothesized that ICU mortality from severe sepsis is associated with distinctive gene expression of extrinsic apoptosis markers.

Methods

A prospective observational study of patients with severe sepsis was performed. Mononuclear cells were isolated from 48 patients with severe sepsis. Total RNA was extracted from samples for day 1 of admission and again on day 7. FADD, caspase 1, 3, 8, and 9 mRNA was quantified with quantitative real-time polymerase chain reaction (qRT-PCR). Standard demographic and outcome data were recorded. Between-group comparisons were performed by Wilcoxon rank sum test. All values are stated as median and interquartile range.

Results

Sixteen of the 48 patients died in the ICU. Caspase 9 mRNA copy numbers were significantly increased on day 7 in the survivor group (5.4 × 106; 7.4 × 106 to 8.9 × 106) compared with death in the ICU group (1.9 × 106; 3.0 × 106 to 1.2 × 106) P = 0.001. FADD, caspase 1, 3 and 8 mRNA copy numbers were not significantly different between patients who died and those discharged from the ICU on either day 1 or day 7 of admission.

Conclusions

Caspase 9 may be an important regulator of apoptotic mechanisms in humans with late sepsis. Pro-apoptotic mechanisms may have a role in the resolution of severe sepsis.

Declarations

Acknowledgements

This study is funded by the Association of Anaesthetists of Great Britain and Ireland and the Intensive Care Society Ireland.

Authors’ Affiliations

(1)
St James Hospital
(2)
Trinity College

References

  1. Oberholzer C, et al.: Apoptosis in sepsis: a new target for therapeutic exploration. FASEB J 2001, 15: 879-892. 10.1096/fj.00-058revPubMedView ArticleGoogle Scholar
  2. Hotchkiss R, et al.: Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochrondrial pathways. J Immunol 2005, 174: 5110-5118.PubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd. 2010

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