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Volume 15 Supplement 3

Sepsis 2011

  • Poster presentation
  • Open Access

Effect of low-dose steroid on NF-κB and caspase-3 intestinal expression in a sepsis mouse model

  • 1, 2,
  • 1, 2,
  • 3 and
  • 3
Critical Care201115 (Suppl 3) :P44

https://doi.org/10.1186/cc10413

©  Guntur et al. 2011

  • Published:

Keywords

  • Proinflammatory Cytokine
  • Intestinal Tract
  • Effector Caspase
  • Acute Inflammatory Response
  • Sepsis Group

Introduction

The use of low-dose corticosteroids in sepsis early stages is still debated. The association of LPS-LBP complexes to CD14 receptors and will interact with TLR4 to induce NF-κB as a signal and transcription of proinflammatory cytokines [1, 2]. Excessive production of inflammatory cytokines will cause activation of SIRS, especially in gut-associated lymphoid tissues [3], which induces metabolic changes leading to apoptosis network, MOF, septic shock and death [3–5]. Changes in apoptosis are mediated by caspases, including caspase-3 that acts as an effector caspase [6, 7]. Low-dose corticosteroids can inhibit the production of proinflammatory cytokines, production of inflammatory mediators, and lower adhesion of leukocytes to the endothelium [8].

Objective

The aim of this study was to analyse NF-κB and caspase-3 intestinal expression, and also survival from use of low-dose steroid in the early stages of sepsis in the Balb/C mouse model of sepsis.

Methods

Male Balb/C mice were inoculated with lipopolysaccharide for the sepsis mouse model. Sepsis mouse model grouping was to a sepsis group (Group I) and to sepsis with steroid (methylprednisolone 1 to 1.5 mg/kg BW/day) (Group II). Detection of intestinal NF-κB and caspase-3 expression used the immunohistochemistry technique on days 1, 3, 5 and 7. Survival was seen until the 7th day. The two-tailed Fisher exact test for the analysis of mortality, independent-sample t test for intestinal NF-κB and caspase-3 expression, and P < 0.05 were used to determine significant differences.

Results

Acute inflammatory response occurs in the early stages of sepsis (the first 5 days of exposure) and the process of death occurs in advanced stages of sepsis (after the first 5 days of exposure) [9]. This study shows that the use of low-dose corticosteroids in sepsis early stages (first 5 days) significantly inhibited the expression of NF-κB (see Table 1), so cytokine production of proinflammatory cytokines was not excessive. Reduced product proinflammatory cytokines would reduce the expression of intestinal caspase-3 (see Table 2), which will reduce the excessive apoptosis in the intestinal tract. Decreased expression of NF-κB and caspase-3 in the intestinal tract would further reduce the excessive mucosal cell death. This situation will block the destruction and disruption of mucosal defense function of the digestive tract, thereby increasing immune response. The end result will be seen that low-dose corticosteroids can reduce mortality. This study found dead animals for Group I were 70%, while Group II were 10% (P = 0.020).
Table 1

NF-κB intestinal expression

 

Amount of cell expression

 

Day

Group I

Group II

Pvalue

1

17.5 ± 4.7

10.8 ± 3.6

0.019

3

26.5 ± 4.4

15.8 ± 3.6

0.001

5

39.3 ± 4.1

31.2 ± 7.0

0.033

7

54.8 ± 9.6

50.5 ± 10.7

0.476

Data presented as mean ± standard deviation.

Table 2

Caspase-3 intestinal expression

 

Amount of cell expression

 

Day

Group I

Group II

Pvalue

1

8.5 ± 2.9

4.3 ± 1.9

0.014

3

14.7 ± 3.1

9.8 ± 2.2

0.012

5

33.2 ± 8.3

12.8 ± 4.5

0.000

7

42.3 ± 3.2

37.7 ± 8.2

0.336

Data presented as mean ± standard deviation.

Conclusion

Low-dose steroids can reduce NF-κB and caspase-3 intestinal expression and also mortality in early sepsis.

Declarations

Acknowledgements

The authors thank the Faculty of Medicine, University of Sebelas Maret for their financial support and assistance given in this study.

Authors’ Affiliations

(1)
Indonesian Society for the Study of Tropical Medicine and Infectious Diseases, Surakarta, Indonesia
(2)
Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
(3)
Indonesian Society for the Study of Tropical Medicine and Infectious Diseases, Jakarta, Indonesia

References

  1. Hongwei Q, Cynthia AW, Sun JL, Xueyan Z, Etty NB: LPS induces CD40 gene expression through the activation of NF-κB and STAT-1α in macrophages and microglia. Blood. 2005, 106: 3114-3122. 10.1182/blood-2005-02-0759.View ArticleGoogle Scholar
  2. Kristine MJ, Sarah BL, Anncatrine LP, Jesper EO, Thomas B: Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from gram negative sepsis. BMC Infect Dis. 2007, 7: 108-10.1186/1471-2334-7-108.View ArticleGoogle Scholar
  3. Arul MC, Markus HL, Chandan KS, Terrence RB, Sunita SS, Vidya JS, Vaishalee AP, Peter AW: Molecular signatures of sepsis multiorgan gene expression profiles of systemic inflammation. Am J Pathol. 2001, 159: 1199-1209. 10.1016/S0002-9440(10)62505-9.View ArticleGoogle Scholar
  4. Elena GR, Alejo C, Gema R, Mario D: Cortistatin, a new anti-inflammatory peptide with therapeutic effect on lethal endotoxemia. J Exp Med. 2006, 203: 563-571. 10.1084/jem.20052017.View ArticleGoogle Scholar
  5. Javier C, José Y, David HE, Yolanda M, Ruben M, Isabel A, Antonia M, Pascual P, Vicente V: Role of lipopolysaccharide and cecal ligation and puncture on blood coagulation and inflammation in sensitive and resistant mice models. Am J Pathol. 2005, 166: 1089-1098. 10.1016/S0002-9440(10)62329-2.View ArticleGoogle Scholar
  6. Chung CS, Chaudry IH, Ayala A: The apoptotic response of the lymphoid immune system to trauma, shock and sepsis. Yearbook of Intensive Care and Emergency Medicine. Edited by: Vincent JL. 2000, Berlin: Spinger-Verlag, 27-40.Google Scholar
  7. Chung CS, Song GY, Lomas J, Simms HH, Chaudry IH, Ayala A: Inhibition of Fas/Fas ligand signaling improves septic survival: differential effects on macrophage apoptotic and functional capacity. J Leukoc Biol. 2003, 74: 344-351. 10.1189/jlb.0102006.View ArticlePubMedGoogle Scholar
  8. Annane D, Caillon DM: Corticosteroid in sepsis: from bench to bedside. Shock. 2003, 20: 197-207. 10.1097/01.shk.0000079423.72656.2f.View ArticlePubMedGoogle Scholar
  9. Xiao H, Siddiqui J, Remick DG: Mechanisms of mortality in early and late sepsis. Infection Immunity. 2006, 74: 5227-5235. 10.1128/IAI.01220-05.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Guntur et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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