Volume 11 Supplement 4

Sepsis 2007

Open Access

Tolerance to lipopolysaccharide regulates apoptosis in B lymphocytes

  • Edielle de Sant Anna Melo1,
  • Renata Gorjao1,
  • Ruy Curi1,
  • Irineu Tadeu Velasco1 and
  • Francisco Garcia Soriano1
Critical Care200711(Suppl 4):P21

https://doi.org/10.1186/cc6000

Published: 26 September 2007

Background

The most important event determining sepsis evolution is immune system cell apoptosis, the immune cell elimination compromises the host effective response, and prevention of apoptosis events improve survival in sepsis models. Our objective was to identify whether lipopolysaccharide (LPS) tolerance regulates apoptotic genes and caspase pathway.

Materials and methods

Male Balb-C mice received LPS (1 mg/kg), a tolerant dose, and controls received 0.9% physiological serum during 5 days, both receiving on day 7 a LPS lethal dose (20 mg/kg). Control, 2 and 4 hours after lethal dose, IL-10, IL-6, IL-1β, TNFα and MIP2 were measured by ELISA. Splenic B lymphocytes were separated through magnetic beads and genes were analyzed by microarray, comparing control and tolerant groups. The tolerant and control groups were followed during 5 days to analyze survival.

Results

See Table 1. The mRNA of caspases 2, 7, 8 and 11, Bid, Apaf-1 and FAS genes were reduced in the tolerant mice. The IL-6 levels reduced in the tolerant mice (724 ± 15 pg/ml) versus control mice (1,488 ± 96 pg/ml) in 2 hours. IL-1β was reduced at 0 hours and at 4 hours in the tolerant group (657 ± 25 pg/ml) versus control (1,117 ± 20 pg/ml). MIP2 also showed a reduction at 4 hours in tolerant (1,803 ± 159 pg/ml) versus control mice (2,173 ± 252 pg/ml). The tolerant animals had 100% survival, controls had zero survival. In all mentioned data, P < 0.05.
Table 1

Genic expression of apoptosis in tolerance to lipopolysaccharide

Genebank analysis number

Name

Ratioa

X92346

TNF receptor-associated factor 4 (TRAF4)

3.8

U06948

Fas antigen ligand (FASL)

4.5

U37522

TNF-related apoptosis-inducing ligand (TRAIL)

3.9

M83649

Fas I receptor

4.8

U88990

Inhibitor of apoptosis protein 3

Down

D28492

Caspase 2 precursor

Up

U39613

Caspase 7, apoptosis-related cysteine protease

Up

U59463

Caspase 11

3.4

U13021

Caspase 2, apoptosis-related cysteine protease

Up

AF064071

Apoptotic protease activating factor 1

Up

U39643

Fas-associated factor 1

Up

X67914

Programmed cell death 1 protein precursor

Up

NM022684

Bid, apoptotic protease

4.6

XM232860

Caspase 8, apoptosis-related cysteine protease

Up

aRatio = controls/tolerants: down, down to 0.05; up, up to 5.0.

Conclusion

Tolerance was able to reduce cytokine plasma levels, immune cell apoptosis and mortality to LPS lethal doses.

Authors’ Affiliations

(1)
Medical Clinical Department Clinical Emergency – LIM 51, University of São Paulo Medicine School

Copyright

© BioMed Central Ltd 2007

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