IL-1/MyD88-Dependent G-CSF and IL-6 Secretion Mediates Postburn Anemia.

The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion.

Heat-killed probiotic Lactobacillus plantarum affects the function of neutrophils but does not improve survival in murine burn injury.

Probiotics have become of interest as therapeutics in trauma or sepsis-induced inflammation due to their ability to affects the immune response. However, their use is still under debate due to the potential risk of septicemia. Therefore, heat-killed probiotics offer a potential alternative, with recent research suggesting a comparable immunomodulating potential and increased safety.

sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury.

Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue. PUFA-derived oxylipins regulate a variety of biological functions. The cytochrome P450 (CYP450)–formed epoxy fatty acid metabolites of LA (EpOMEs) are hydrolyzed by the soluble epoxide hydrolase enzyme (sEH) to dihydroxyoctadecenoic acids (DiHOMEs).

TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function.

Oxylipins modulate the behavior of immune cells in inflammation. Soluble epoxide hydrolase (sEH) converts anti-inflammatory epoxyeicosatrienoic acid (EET) to dihydroxyeicosatrienoic acid (DHET). An sEH-inhibitor, TPPU, has been demonstrated to ameliorate lipopolysaccharide (LPS)- and sepsis-induced inflammation via EETs.

Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model.

Introduction: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes.

Fibrotic liver has prompt recovery after ischemia-reperfusion injury.

Hepatic ischemia-reperfusion (I/R) is a major complication of liver resection, trauma, and liver transplantation; however, liver repair after I/R in diseased liver has not been studied. The present study sought to determine the manner in which the fibrotic liver repairs itself after I/R. Liver fibrosis was established in mice by CCl administration for 6 wk, and then liver I/R was performed to investigate liver injury and subsequent liver repair in fibrotic and control livers.

Cell-specific regulatory effects of CXCR2 on cholestatic liver injury.

The CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2-/- mice were subjected BDL.

Amitriptyline Treatment Mitigates Sepsis-Induced Tumor Necrosis Factor Expression and Coagulopathy.

During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis-cecal ligation and puncture (CLP).

A Murine Model of Persistent Inflammation, Immune Suppression, and Catabolism Syndrome.

Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen.

Impact of tranexamic acid on coagulation and inflammation in murine models of traumatic brain injury and hemorrhage.

Background: Posttraumatic coagulopathy and inflammation can exacerbate secondary cerebral damage after traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown clinically to reduce mortality in hemorrhaging and head-injured trauma patients and has the potential to mitigate secondary brain injury with its reported antifibrinolytic and antiinflammatory properties. We hypothesized that TXA would improve posttraumatic coagulation and inflammation in a murine model of TBI alone and in a combined injury model of TBI and hemorrhage (TBI/H).

Mechanisms underlying mouse TNF-α stimulated neutrophil derived microparticle generation.

Despite advances in understanding and treatment of sepsis, it remains a disease with high mortality. Neutrophil Derived Microparticles (NDMPs) are present during sepsis and can modulate the immune system. As TNF-α is a cytokine that predominates in the initial stages of sepsis, we evaluated whether and how TNF-α can induce NDMPs in mice.

Roles of hepatocyte and myeloid CXC chemokine receptor-2 in liver recovery and regeneration after ischemia/reperfusion in mice.

Unlabelled: Previous studies have demonstrated the significance of signaling through the CXC chemokine receptor-2 (CXCR2) receptor in the process of recovery and regeneration of functional liver mass after hepatic ischemia/reperfusion (I/R). CXCR2 is constitutively expressed on both neutrophils and hepatocytes; however, the cell-specific roles of this receptor are unknown. In the present study, chimeric mice were created through bone marrow transplantation (BMT) using wild-type and CXCR2-knockout mice, yielding selective expression of CXCR2 on hepatocytes (Hep) and/or myeloid cells (My) in the following combinations: Hep+/My+; Hep-/My+; Hep+/My-; and Hep-/My-.

Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis.

The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance.

T-cell activation differentially mediates the host response to sepsis.

Survival during sepsis requires both swift control of infectious organisms and tight regulation of the associated inflammatory response. As the role of T cells in sepsis is somewhat controversial, we examined the impact of increasing antigen-dependent activation of CD4 T cells in a murine model of cecal ligation and puncture using T-cell receptor transgenic II (OT-II) mice that are specific for chicken ovalbumin (OVA) in the context of major histocompatibility complex II. Here, we injected OT-II mice with 0, 1, or 100 μg of OVA and demonstrate that increased antigen treatment resulted in increased numbers of activated splenic CD4 T cells.

Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction.

Following burn injury, the host is susceptible to bacterial infections normally cleared by healthy patients. We hypothesized that during the systemic immune response that follows scald injury, the host's altered immune status increases infection susceptibility. Using a murine model of scald injury under inhaled anesthesia followed by intraperitoneal infection, we observed increased neutrophil numbers and function at postburn day (PBD) 1 compared with sham-burned and PBD4 mice.

Divergent adaptive and innate immunological responses are observed in humans following blunt trauma.

Background: The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury.

The cannabinoid receptor 2 is critical for the host response to sepsis.

Leukocyte function can be modulated through the cannabinoid receptor 2 (CB2R). Using a cecal ligation and puncture (CLP) model of sepsis, we examined the role of the CB2R during the immune response to an overwhelming infection. CB2R-knock out (KO) mice showed decreased survival as compared with wild-type mice.

Gammadelta T cells mitigate the organ injury and mortality of sepsis.

Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. gammadelta T cells are found largely in epithelial-rich tissues, and previous studies of gammadelta T cells in models of sepsis have yielded divergent results.

CD4-expressing cells are early mediators of the innate immune system during sepsis.

It is well established that the immune response to sepsis is mediated by leukocytes associated with the innate immune system. However, there is an emerging view that T lymphocytes can also mediate this response. Here, we observed a significant depletion of both CD4 and CD8 T cells in human patients after blunt trauma.

Thermal injury elevates the inflammatory monocyte subpopulation in multiple compartments.

Recent publications have demonstrated that human resident and inflammatory monocyte (IM) subpopulations have equivalents in rodents. The effect of thermal injury upon these subpopulations has not been studied. Mice were given a scald burn and killed on postburn days (PBDs) 2, 4, and 8.