Effects of Estrogen on Bacterial Clearance and Neutrophil Response After Combined Burn Injury and Wound Infection.

Females have a higher rate of mortality following burn injury, largely due to differences in sepsis-related mortality. The present study seeks to understand the underpinnings of the estrogen's immunomodulatory effects in a murine model of burn injury and infection. Gonad-intact and ovariectomized female mice were subjected to a 15% total BSA scald injury and then inoculated with 3000 CFU of Pseudomonas aeruginosa by topical application to the wound.

Neutrophil Accumulation in the Small Intestine Contributes to Local Tissue Destruction Following Combined Radiation and Burn Injury.

The threat of nuclear disaster makes combined radiation and burn injury (CRI) a relevant topic when discussing modern trauma, as burn injuries are likely to occur with detonation of a conventional nuclear weapon. Previous studies in a murine model have shown that there is a breakdown of the gut epithelium and subsequent bacterial translocation into mesenteric lymph nodes after CRI. This study examines the early innate immune response of the small intestine after CRI.

Age-related differences in the neutrophil response to pulmonary pseudomonas infection.

Background: Pseudomonas aeruginosa pneumonia is more common and more lethal in the elderly. The immunologic underpinnings of this increased incidence and mortality have not been evaluated, however are assumed to be a complication of age-associated immune dysfunction.

Methods: Young (10-12week old) and aged (18-20month old) BALB/c mice were subjected to intratracheal infection of P.

Intoxication by intraperitoneal injection or oral gavage equally potentiates postburn organ damage and inflammation.

The increasing prevalence of binge drinking and its association with trauma necessitate accurate animal models to examine the impact of intoxication on the response and outcome to injuries such as burn. While much research has focused on the effect of alcohol dose and duration on the subsequent inflammatory parameters following burn, little evidence exists on the effect of the route of alcohol administration. We examined the degree to which intoxication before burn injury causes systemic inflammation when ethanol is given by intraperitoneal (i.

Intestinal barrier disruption as a cause of mortality in combined radiation and burn injury.

Nuclear disaster associated with combined radiation injury (CRI) and trauma or burns results in higher mortality than component injuries. Early death is caused by sequelae of gastrointestinal (GI) leakiness such as bacterial translocation and shock. We developed a murine model to characterize GI injury after CRI and determine the extent of barrier disruption.

Combined radiation and burn injury results in exaggerated early pulmonary inflammation.

Events such as a nuclear meltdown accident or nuclear attack have potential for severe radiation injuries. Radiation injury frequently occurs in combination with other forms of trauma, most often burns. Thus far, combined injury studies have focused mainly on skin wound healing and damage to the gut.

Dysregulation of neutrophil CXCR2 and pulmonary endothelial icam-1 promotes age-related pulmonary inflammation.

We have previously demonstrated that aging is associated with prolonged pulmonary inflammation in a murine model of thermal injury. To further investigate these observations, we examined lung congestion, markers of neutrophil chemotaxis and adhesion, and lung endothelia responses in young and aged mice following burn injury. Analysis of lung tissue and bronchoalveolar lavage fluid 24 hours after injury revealed that more neutrophils accumulated in the lungs of aged mice (p<0.

Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models.

In the elderly patient population, it has become increasingly evident that immune dysregulation is a contributing factor to age-related pathologies and their associated morbidity and mortality. In particular, elderly subjects are plagued by poor responses to infectious challenge and immunization and are at heightened risk for the development of autoimmune, neuroinflammatory and tumor-associated pathologies. Rodent models of aging and age-related disorders have been utilized to better describe how innate immune cell dysfunction contributes to these clinical scenarios.

An improved cell isolation method for flow cytometric and functional analyses of cutaneous wound leukocytes.

Isolation of leukocytes from full-thickness excisional wounds has proven to be a difficult process that results in poor cell yield and holds significant limitations for functional assays. Given the increased interest in the isolation, characterization and functional measurements of wound-derived cell populations, herein we describe a method for preparing wound cell suspensions with an improved yield that enables both phenotypic and functional assessments.

Development of a combined radiation and burn injury model.

Combined radiation and burn injuries are likely to occur after nuclear events, such as a meltdown accident at a nuclear energy plant or a nuclear attack. Little is known about the mechanisms by which combined injuries result in higher mortality than by either insult alone, and few animal models exist for combined radiation and burn injury. Herein, the authors developed a murine model of radiation and scald burn injury.

Prevention of NKT cell activation accelerates cutaneous wound closure and alters local inflammatory signals.

We previously reported that in the absence of NKT cells, wound closure was accelerated in a murine excisional punch wound model. Here, we explored whether purposefully inhibiting NKT cell activation had similar effects on wound closure and the dermal inflammatory response to injury. We found that prevention of NKT cell activation accelerated wound closure in a dose-responsive manner.

Interleukin-6 contributes to age-related alteration of cytokine production by macrophages.

Here, we studied in vitro cytokine production by splenic macrophages obtained from young and aged BALB/c wild type (WT) and IL-6 knockout (IL-6 KO) mice. Relative to macrophages obtained from young WT mice given lipopolysaccharide (LPS), those from aged WT mice had decreased production of proinflammatory cytokines. In contrast, when compared to macrophages from young IL-6 KO mice, LPS stimulation yielded higher levels of these cytokines by cells from aged IL-6 KO mice.

A novel role for NKT cells in cutaneous wound repair.

Here, we report the novel observation that natural killer T (NKT) cells contribute to the cutaneous wound repair process. Using an excisional wound model in wild-type versus NKT cell-deficient mice, this report shows that when NKT cells are absent, initial wound closure is markedly accelerated. We report here for the first time that NKT cells are a significant constituent of early wound inflammation and that they regulate the local production of a key subset of neutrophil and monocyte/macrophage chemokines, as well as TGF-β1 content and collagen deposition.

Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors.

Aging affects every innate immune cell, including changes in cell numbers and function. Defects in the function of some cells are intrinsic, whereas for other cells, defects are extrinsic and possibly the consequence of the complex interactions with other cell types or the environmental milieu that is altered with aging. Abnormal function contributes to worsened outcomes after injury or infection and leads to diseases observed in the elderly.

Prevention of injury-induced suppression of T-cell immunity by the CD1d/NKT cell-specific ligand alpha-galactosylceramide.

Infection, sepsis, and multiple organ failure continue to be significant factors leading to morbidity and mortality after severe injury. Studies by our laboratory and others have identified injury-induced defects in both innate and adaptive components of host defense. We previously reported that CD1d-restricted natural killer T (NKT) cells actively suppress effector T-cell immunity after burn injury via production of excess IL-4 and failure to produce IFN-gamma.

The effects of microenvironment and internal programming on plasma cell survival.

Two populations of plasma cells (PCs) are formed after immunization. A short-lived population in the spleen and lymph nodes provides rapid protection. A long-lived population, mainly in the bone marrow, provides lasting immunity.

Injury-induced suppression of effector T cell immunity requires CD1d-positive APCs and CD1d-restricted NKT cells.

Overwhelming infection remains the leading cause of death from serious burn injury despite recent advances in the care of burn patients and a better understanding of immune and inflammatory consequences of injury. In this study, we report a critical requirement for CD1d-restricted NKT cells and CD1d expression by APCs in the immune dysfunction that occurs early after burn injury. Using a well-established murine scald injury model with BALB/c and BALB/c CD1d knockout mice, we investigated whether peripheral T cell immunity was affected by the presence or absence of CD1d-restricted NKT cells in the early stages after injury.

CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity.

NKT cells are known to regulate effector T cell immunity during tolerance, autoimmunity, and antitumor immunity. Whether age-related changes in NKT cell number or function occur remains unclear. Here, we investigated whether young vs aged (3 vs 22 mo old) mice had different numbers of CD1d-restricted NKT cells and whether activation of NKT cells by CD1d in vivo contributed to age-related suppression of T cell immunity.

Dynamic control of B lymphocyte development in the bursa of fabricius.

The chicken is a foundational model for immunology research and continues to be a valuable animal for insights into immune function. In particular, the bursa of Fabricius can provide a useful experimental model of the development of B lymphocytes. Furthermore, an understanding of avian immunity has direct practical application since chickens are a vital food source.