IL-10 deficiency augments acute lung but not liver injury in hemorrhagic shock

Kobbe, Philipp; Stoffels, Burkhard; Schmidt, Joachim; Tsukamoto, Takeshi; Gutkin, Dmitry W.; Bauer, Anthony J.; Pape, Hans-Christian

doi:10.1016/j.cyto.2008.10.004

Cited by 26 publications

(25 citation statements)

References 34 publications

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“…Our ThS model could also be an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, as it elicits distinct responses that differ from other forms of shock [7,15]. Moreover, the development of knockout and transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up-and downregulation of signal transduction after ThS [14,19]. ThS patients tend to be at risk of developing hypovolemia, with subsequent tissue malperfusion and organ dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

et al. 2012

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This study established an experimental mouse model of trauma-hemorrhagic shock (THS). THS-induced mice (C57BL/6J, n=33) were subjected to femoral fracture, ischemia for 90 min, and resuscitation for 15 min. The sham-operated mice (C57BL/6J, n=33) underwent the same anesthetic and surgical procedures, but neither trauma-hemorrhage nor fluid resuscitation were performed. Mean arterial pressure (MAP) and microvascular tissue perfusion over the small intestine, liver, and left kidney were longitudinally measured in all mice. Blood was collected for analysis at baseline and 3, 6, 12, and 24 h post resuscitation, and the small intestine, liver, and left kidney were resected for hematoxylin and eosin staining 24 h post resuscitation. Compared with the sham group, MAP and microvascular tissue perfusion over the small intestine, liver, and left kidney were all significantly reduced in the THS group at the end of hemorrhage. Following resuscitation, no significant differences were observed between the groups. THS induction was associated with significantly increased plasma concentrations of Cr, AST, CPK, IL-6, IL-10, and TNF-α from the baseline values by two-to three-fold after the hemorrhage phase, and THS-induced mice demonstrated significantly increased histological injury scores. The rapid drop in MAP and microvascular tissue perfusion observed following THS induction, and the gradual recovery post resuscitation, reflects the successful establishment of a THS experimental mouse model.

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Section: Discussionmentioning

confidence: 99%

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

et al. 2012

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“…MCP-1 has been underscored as a contributor to the heightened systemic inflammation seen in autoimmune diseases (19,39). Also, MCP-1 levels are associated with increased inflammation and macrophage infiltration in numerous models of acute lung injury (27,41,48), including those with intratracheal LPS (23,24). Interestingly, pulmonary vascular permeability after rat renal ischemia was significantly abrogated by a macrophage pacifant (28).…”

Section: Discussionmentioning

confidence: 99%

Antecedent acute kidney injury worsens subsequent endotoxin-induced lung inflammation in a two-hit mouse model

Basu

Donaworth²,

Wheeler³

et al. 2011

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) contributes greatly to morbidity and mortality in critically ill adults and children. Patients with AKI who subsequently develop lung injury are known to suffer worse outcomes compared with patients with lung injury alone. Isolated experimental kidney ischemia alters distal lung water balance and capillary permeability, but the effects of such an aberration on subsequent lung injury are unknown. We present a clinically relevant two-hit murine model wherein a proximal AKI through bilateral renal ischemia (30 min) is followed by a subsequent acute lung injury (ALI) via intratracheal LPS endotoxin (50 g at 24 h after surgery). Mice demonstrated AKI by elevation of serum creatinine and renal histopathological damage. Mice with ALI and preexisting AKI had increased lung neutrophilia in bronchoalveolar lavage fluid and by myeloperoxidase activity over Sham-ALI mice. Additionally, lung histopathological damage was greater in ALI mice with preexisting AKI than Sham-ALI mice. There was uniform elevation of monocyte chemoattractant protein-1 in kidney, serum, and lung tissue in animals with both AKI and ALI over those with either injury alone. The additive lung inflammation after ALI with antecedent AKI was abrogated in MCP-1-deficient mice. Taken together, our two-hit model demonstrates that kidney injury may prime the lung for a heightened inflammatory response to subsequent injury and MCP-1 may be involved in this model of kidney-lung cross talk. The model holds clinical relevance for patients at risk of lung injury after ischemic injury to the kidney.

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“…1,2,3,4,5 These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). 6,7,8,9 It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. 10 This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions.…”

Section: Introductionmentioning

confidence: 99%

“…22,23,24,25 The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma 26,27,28,29,30 .There are numerous resuscitation methods (R) in association with HS and trauma. 31,32,33,34 A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation.…”

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confidence: 99%

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Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

Kohut

Darwiche

Brumfield

et al. 2011

JoVE

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It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1,2,3,4,5 These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). 6,7,8,9 It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. 10 This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions. 11,12,13 Advances in the assessment of biological systems, i.e. Systems Biology have enabled the scientific community to further understand complex physiologic networks and cellular communication patterns. 14 HemorrhagicShock has proven to be a vital tool for unveiling these cellular communication patterns as they relate to immune function. 15,16,17,18 This procedure can be mastered! This procedure can also be used as either a fixed volume or fixed pressure approach. We adapted this technique in the murine model to enhance research in innate and adaptive immune function. 19,20,21 Due to their small size HS in mice presents unique challenges. However due to the many available mouse strains, this species represents an unparalleled resource for the study of the biologic responses. The HS model is an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, i.e. DAMP and PAMP upregulation as it elicits distinct responses that differ from other forms of shock. 22,23,24,25 The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma 26,27,28,29,30 .There are numerous resuscitation methods (R) in association with HS and trauma. 31,32,33,34 A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation. 35,36,38 This method of resuscitation is proven to be effective in evaluating the effects of HS and trauma 38,39 .

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IL-10 deficiency augments acute lung but not liver injury in hemorrhagic shock

Cited by 26 publications

References 34 publications

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

Antecedent acute kidney injury worsens subsequent endotoxin-induced lung inflammation in a two-hit mouse model

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

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