Open Access Highly Accessed Research article

Detrimental effect of apoptosis of lymphocytes at an early time point of experimental abdominal sepsis

Stefanos Atmatzidis1, Ioannis M Koutelidakis1, Grigorios Chatzimavroudis1, Antigone Kotsaki2, Konstantinos Louis2, Aikaterini Pistiki2, Athina Savva2, Anastasia Antonopoulou2, Konstantinos Atmatzidis1 and Evangelos J Giamarellos-Bourboulis2*

Author Affiliations

1 2nd Department of Surgery, University of Thessaloniki, Medical School, Thessaloniki, Greece

2 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece

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BMC Infectious Diseases 2011, 11:321  doi:10.1186/1471-2334-11-321

Published: 20 November 2011

Abstract

Background

Apoptosis of lymphocytes is considered a late sequelum in the sepsis cascade. The role of apoptosis of lymphocytes as a driver of final outcome was investigated.

Methods

Abdominal sepsis was induced after cecal ligation and puncture (CLP) in 31 rabbits. Blood was sampled at serial time intervals and peripheral blood mononuclear cells (PBMCs) were isolated. Apoptosis of lymphocytes and monocytes was measured through flow cytometric analysis. PBMCs were stimulated with LPS and Pam3Cys for the release of tumor necrosis factor-alpha (TNFα). Tissue bacterial growth was quantitatively measured. In a second set of experiments, CLP was performed in another 40 rabbits; 20 received single intravenous infusions of ciprofloxacin and of metronidazole 4 hours after surgery.

Results

Animals were divided into two groups based on the percentage of lymphocyte apoptosis at 4 hours after surgery; less than or equal to 32% and more than 32%. Survival of the former was shorter than the latter (p: 0.017). Tissue growth was similar between groups. Apoptosis of lymphocytes and of monocytes was lower in the former group over follow-up. Release of ΤNFα did not differ. The above findings on survival were repeated in the second set of experiments. Administration of antimicrobials prolonged survival of the former group (p: 0.039) but not of the latter group (pNS).

Conclusions

Lymphocyte apoptosis at an early time point of experimental peritonitis is a major driver for death. A lower percentage of apoptosis leads earlier to death. Antimicrobials were beneficial even at that disease state.

Keywords:
apoptosis; abdominal sepsis; survival; lymphocytes; antimicrobials