Exposure to Bacterial DNA Before Hemorrhagic Shock Strongly Aggravates Systemic Inflammation and Gut Barrier Loss via an IFN-gamma-Dependent Route

M.D.P. Luyer, W.A. Buurman, M. Hadfoune, T.G.A.M. Wolfs, C. van 't Veer, J.A. Jacobs, C.H. Dejong, J.W. Greve

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21 Citations (Scopus)

Abstract

OBJECTIVE:: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension. SUMMARY BACKGROUND DATA:: Bacterial infection may contribute to development of inflammatory complications following major surgery; however, the pathogenesis is not clear. A common denominator of bacterial infection is bacterial DNA characterized by unmethylated CpG motifs. Recently, it has been shown that bacterial DNA or synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are immunostimulatory leading to release of inflammatory mediators. METHODS:: Rats were exposed to CpG-ODN prior to a nonlethal hemorrhagic shock. The role of interferon-gamma (IFN-gamma) was investigated by administration of anti IFN-gamma antibodies. RESULTS:: Exposure to CpG-ODN prior to hemorrhagic shock significantly augmented shock-induced release of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin (IL)-6 (P < 0.05), and nitrite levels (P < 0.05), while there was a defective IL-10 response (P < 0.05). Simultaneously, expression of Toll-like receptor (TLR) 4 in the liver was markedly enhanced. Furthermore, intestinal permeability for HRP significantly increased and bacterial translocation was enhanced in hemorrhagic shock rats pretreated with CpG-ODN. Interestingly, inhibition of IFN-gamma in CpG-treated animals reduced TNF-alpha (P < 0.05), IL-6 (P < 0.05), nitrite (P < 0.05), and intestinal permeability following hemorrhagic shock (P < 0.05) and down-regulated expression of TLR4. CONCLUSION:: Exposure to bacterial DNA strongly aggravates the inflammatory response, disrupts the intestinal barrier, and up-regulates TLR4 expression in the liver following hemorrhagic shock. These effects are mediated via an IFN-gamma-dependent route. In the clinical setting, bacterial DNA may be important in development of inflammatory complications in surgical patients with bacterial infection.
Original languageEnglish
Pages (from-to)795-802
JournalAnnals of Surgery
Volume245
Issue number5
DOIs
Publication statusPublished - 1 Jan 2007

Cite this

@article{3a458e66f60f4b60af7b03d0f3af29ff,
title = "Exposure to Bacterial DNA Before Hemorrhagic Shock Strongly Aggravates Systemic Inflammation and Gut Barrier Loss via an IFN-gamma-Dependent Route",
abstract = "OBJECTIVE:: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension. SUMMARY BACKGROUND DATA:: Bacterial infection may contribute to development of inflammatory complications following major surgery; however, the pathogenesis is not clear. A common denominator of bacterial infection is bacterial DNA characterized by unmethylated CpG motifs. Recently, it has been shown that bacterial DNA or synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are immunostimulatory leading to release of inflammatory mediators. METHODS:: Rats were exposed to CpG-ODN prior to a nonlethal hemorrhagic shock. The role of interferon-gamma (IFN-gamma) was investigated by administration of anti IFN-gamma antibodies. RESULTS:: Exposure to CpG-ODN prior to hemorrhagic shock significantly augmented shock-induced release of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin (IL)-6 (P < 0.05), and nitrite levels (P < 0.05), while there was a defective IL-10 response (P < 0.05). Simultaneously, expression of Toll-like receptor (TLR) 4 in the liver was markedly enhanced. Furthermore, intestinal permeability for HRP significantly increased and bacterial translocation was enhanced in hemorrhagic shock rats pretreated with CpG-ODN. Interestingly, inhibition of IFN-gamma in CpG-treated animals reduced TNF-alpha (P < 0.05), IL-6 (P < 0.05), nitrite (P < 0.05), and intestinal permeability following hemorrhagic shock (P < 0.05) and down-regulated expression of TLR4. CONCLUSION:: Exposure to bacterial DNA strongly aggravates the inflammatory response, disrupts the intestinal barrier, and up-regulates TLR4 expression in the liver following hemorrhagic shock. These effects are mediated via an IFN-gamma-dependent route. In the clinical setting, bacterial DNA may be important in development of inflammatory complications in surgical patients with bacterial infection.",
author = "M.D.P. Luyer and W.A. Buurman and M. Hadfoune and T.G.A.M. Wolfs and {van 't Veer}, C. and J.A. Jacobs and C.H. Dejong and J.W. Greve",
year = "2007",
month = "1",
day = "1",
doi = "10.1097/01.sla.0000251513.59983.3b",
language = "English",
volume = "245",
pages = "795--802",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "5",

}

Exposure to Bacterial DNA Before Hemorrhagic Shock Strongly Aggravates Systemic Inflammation and Gut Barrier Loss via an IFN-gamma-Dependent Route. / Luyer, M.D.P.; Buurman, W.A.; Hadfoune, M.; Wolfs, T.G.A.M.; van 't Veer, C.; Jacobs, J.A.; Dejong, C.H.; Greve, J.W.

In: Annals of Surgery, Vol. 245, No. 5, 01.01.2007, p. 795-802.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Exposure to Bacterial DNA Before Hemorrhagic Shock Strongly Aggravates Systemic Inflammation and Gut Barrier Loss via an IFN-gamma-Dependent Route

AU - Luyer, M.D.P.

AU - Buurman, W.A.

AU - Hadfoune, M.

AU - Wolfs, T.G.A.M.

AU - van 't Veer, C.

AU - Jacobs, J.A.

AU - Dejong, C.H.

AU - Greve, J.W.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - OBJECTIVE:: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension. SUMMARY BACKGROUND DATA:: Bacterial infection may contribute to development of inflammatory complications following major surgery; however, the pathogenesis is not clear. A common denominator of bacterial infection is bacterial DNA characterized by unmethylated CpG motifs. Recently, it has been shown that bacterial DNA or synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are immunostimulatory leading to release of inflammatory mediators. METHODS:: Rats were exposed to CpG-ODN prior to a nonlethal hemorrhagic shock. The role of interferon-gamma (IFN-gamma) was investigated by administration of anti IFN-gamma antibodies. RESULTS:: Exposure to CpG-ODN prior to hemorrhagic shock significantly augmented shock-induced release of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin (IL)-6 (P < 0.05), and nitrite levels (P < 0.05), while there was a defective IL-10 response (P < 0.05). Simultaneously, expression of Toll-like receptor (TLR) 4 in the liver was markedly enhanced. Furthermore, intestinal permeability for HRP significantly increased and bacterial translocation was enhanced in hemorrhagic shock rats pretreated with CpG-ODN. Interestingly, inhibition of IFN-gamma in CpG-treated animals reduced TNF-alpha (P < 0.05), IL-6 (P < 0.05), nitrite (P < 0.05), and intestinal permeability following hemorrhagic shock (P < 0.05) and down-regulated expression of TLR4. CONCLUSION:: Exposure to bacterial DNA strongly aggravates the inflammatory response, disrupts the intestinal barrier, and up-regulates TLR4 expression in the liver following hemorrhagic shock. These effects are mediated via an IFN-gamma-dependent route. In the clinical setting, bacterial DNA may be important in development of inflammatory complications in surgical patients with bacterial infection.

AB - OBJECTIVE:: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension. SUMMARY BACKGROUND DATA:: Bacterial infection may contribute to development of inflammatory complications following major surgery; however, the pathogenesis is not clear. A common denominator of bacterial infection is bacterial DNA characterized by unmethylated CpG motifs. Recently, it has been shown that bacterial DNA or synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are immunostimulatory leading to release of inflammatory mediators. METHODS:: Rats were exposed to CpG-ODN prior to a nonlethal hemorrhagic shock. The role of interferon-gamma (IFN-gamma) was investigated by administration of anti IFN-gamma antibodies. RESULTS:: Exposure to CpG-ODN prior to hemorrhagic shock significantly augmented shock-induced release of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin (IL)-6 (P < 0.05), and nitrite levels (P < 0.05), while there was a defective IL-10 response (P < 0.05). Simultaneously, expression of Toll-like receptor (TLR) 4 in the liver was markedly enhanced. Furthermore, intestinal permeability for HRP significantly increased and bacterial translocation was enhanced in hemorrhagic shock rats pretreated with CpG-ODN. Interestingly, inhibition of IFN-gamma in CpG-treated animals reduced TNF-alpha (P < 0.05), IL-6 (P < 0.05), nitrite (P < 0.05), and intestinal permeability following hemorrhagic shock (P < 0.05) and down-regulated expression of TLR4. CONCLUSION:: Exposure to bacterial DNA strongly aggravates the inflammatory response, disrupts the intestinal barrier, and up-regulates TLR4 expression in the liver following hemorrhagic shock. These effects are mediated via an IFN-gamma-dependent route. In the clinical setting, bacterial DNA may be important in development of inflammatory complications in surgical patients with bacterial infection.

U2 - 10.1097/01.sla.0000251513.59983.3b

DO - 10.1097/01.sla.0000251513.59983.3b

M3 - Article

VL - 245

SP - 795

EP - 802

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 5

ER -