Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β<sub>2</sub>-microgloblin knockout mice

Enoh, Victor T; Chen, Lin; Varma, Tushar K.; Sherwood, Edward R.

doi:10.1152/ajpgi.00338.2005

Cited by 8 publications

(5 citation statements)

References 38 publications

(45 reference statements)

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“…Several studies demonstrated that bacterial translocation is an important initiating mechanism for the induction of systemic inflammation and organ injury after CLP as removal of the cecal contents or treatment with powerful antibiotics reduce mortality and organ dysfunction (12,13). We showed in the present study that high bacterial counts were observed in blood and peritoneal cavity (Fig.…”

Section: Markers Of Organ Injury and Dysfunction Markers Of Systemsupporting

confidence: 63%

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

Lee

Kim²,

Joo³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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The role of A3 adenosine receptors (ARs) in sepsis and inflammation is controversial. In this study, we determined the effects of A3AR modulation on mortality and hepatic and renal dysfunction in a murine model of sepsis. To induce sepsis, congenic A3AR knockout mice (A3AR KO) and wild-type control (A3AR WT) mice were subjected to cecal ligation and double puncture (CLP). A3AR KO mice had significantly worse 7-day survival compared with A3AR WT mice. A3AR KO mice also demonstrated significantly higher elevations in plasma creatinine, alanine aminotransferase, aspartate aminotransferase, keratinocyte-derived chemokine, and TNF-alpha 24 h after induction of sepsis compared with A3AR WT mice. Renal cortices from septic A3AR KO mice exhibited increased mRNA encoding proinflammatory cytokines and enhanced nuclear translocation of NF-kB compared with samples from A3AR WT mice. A3AR WT mice treated with N6-(3-iodobenzyl)ADO-5'N-methyluronamide (IB-MECA; a selective A3AR agonist) or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191; a selective A3AR antagonist) had improved or worsened 7-day survival after induction of sepsis, respectively. Moreover, A3AR WT mice treated with IB-MECA or MRS-1191 showed acutely improved or worsened, respectively, renal and hepatic function following CLP. IB-MECA significantly reduced mortality in mice lacking the A1AR or A2aAR but not the A3AR, demonstrating specificity of IB-MECA in activating A3ARs and mediating protection against sepsis-induced mortality. We conclude that endogenous or exogenous A3AR activation confers significant protection from murine septic peritonitis primarily by attenuating the hyperacute inflammatory response in sepsis.

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Section: Markers Of Organ Injury and Dysfunction Markers Of Systemsupporting

confidence: 63%

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

Lee

Kim²,

Joo³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Our studies using ␤ 2 -microglobulin knockout mice show decreased systemic inflammation, less cardiovascular dysfunction, and improved survival after CLP, compared with wildtype controls (11)(12)(13). However, ␤ 2 -microglobulin knockout mice have multiple immunological defects in addition to NKT cell deficiency (14,15).…”

mentioning

confidence: 61%

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Etogo

Nunez

Chen

et al. 2008

The Journal of Immunology

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Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80+GR-1−) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.

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“…In addition, the inclusion of antibiotics in these experimental animal models has varied tremendously with regard to the type of antibiotic, dose, route, and even dosing schedule. Some studies demonstrated improved outcomes (16,17,30,31) or a delay in mortality (32) after CLP in the presence of antibiotics, whereas other studies did not show an improved survival rate (33). Thus, the efficacy of antibiotic treatment in an experimental murine model remains unclear.…”

Section: Figmentioning

confidence: 99%

“…In the present study, we evaluated systematically the contribution of antibiotics in an acute model of sepsis induced by CLP. We used imipenem as the antibiotic of choice for its broad spectrum, covering most enteric organisms, and because it was previously used in various studies (16,17,(30)(31)(32)(33). We did not observe any improvement in survival after CLP by using a variety of antibiotic treatment protocols, including periprocedural, preprocedural, multiple-interval-dosing postprocedural, and even intracecal protocols.…”

Section: Figmentioning

confidence: 99%

Why Antibiotic Treatment Is Not Enough for Sepsis Resolution: an Evaluation in an Experimental Animal Model

et al. 2017

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Sepsis remains a major health problem at the levels of mortality, morbidity, and economic burden to the health care system, a condition that is aggravated by the development of secondary conditions such as septic shock and multiple-organ failure. Our current understanding of the etiology of human sepsis has advanced, at least in part, due to the use of experimental animal models, particularly the model of cecum ligation and puncture (CLP). Antibiotic treatment has been commonly used in this model to closely mirror the treatment of human septic patients. However, whether their use may obscure the elucidation of the cellular and molecular mechanisms involved in the septic response is questionable. The objective of the present study was to determine the effect of antibiotic treatment in the outcome of a fulminant model of CLP. Various dosing strategies were used for the administration of imipenem, which has broad-spectrum coverage of enteric bacteria. No statistically significant differences in the survival of mice were observed between the different antibiotic dosing strategies and no treatment, suggesting that live bacteria may not be the only factor inducing septic shock. To further investigate this hypothesis, mice were challenged with sterilized or unsterilized cecal contents. We found that exposure of mice to sterilized cecal contents also resulted in a high mortality rate. Therefore, it is possible that bacterial debris, apart from bacterial proliferation, triggers a septic response and contributes to mortality in this model, suggesting that additional factors are involved in the development of septic shock.

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Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

Cited by 8 publications

References 38 publications

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Why Antibiotic Treatment Is Not Enough for Sepsis Resolution: an Evaluation in an Experimental Animal Model

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Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice

Cited by 8 publications

References 38 publications

A3adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

A3adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Why Antibiotic Treatment Is Not Enough for Sepsis Resolution: an Evaluation in an Experimental Animal Model

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Product

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Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis

A₃adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis