Delay in neutrophil clearance contributes to intestinal tissue damage following a combined insult of alcohol intoxication and burn injury

Disruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence of this high mitotic activity, mucosal surfaces are frequently targeted by anticancer therapies, leading to dose-limiting side effects. The cellular mechanisms that control tissue protection and mucosal healing in response to intestinal damage remain poorly understood. Type 3 innate lymphoid cells (ILC3s) are regulators of homeostasis and tissue responses to infection at mucosal surfaces. We now demonstrate that ILC3s are required for epithelial activation and proliferation in response to small intestinal tissue damage induced by the chemotherapeutic agent methotrexate. Multiple subsets of ILC3s are activated after intestinal tissue damage, and in the absence of ILC3s, epithelial activation is lost, correlating with increased pathology and severe damage to the intestinal crypts. Using ILC3-deficient Lgr5 reporter mice, we show that maintenance of intestinal stem cells after damage is severely impaired in the absence of ILC3s or the ILC3 signature cytokine IL-22. These data unveil a novel function of ILC3s in limiting tissue damage by preserving tissue-specific stem cells.

Download Full-text

ERK and Not p38 Pathway Is Required for IL-12 Restoration of T Cell IL-2 and IFN-γ in a Rodent Model of Alcohol Intoxication and Burn Injury

The Journal of Immunology ◽

10.4049/jimmunol.0804103 ◽

2009 ◽

Vol 183 (6) ◽

pp. 3955-3962 ◽

Cited By ~ 16

Author(s):

Xiaoling Li ◽

Irshad H. Chaudry ◽

Mashkoor A. Choudhry

Keyword(s):

T Cell ◽

Burn Injury ◽

Alcohol Intoxication ◽

Rodent Model ◽

Ifn Γ ◽

P38 Pathway

Download Full-text

Quantifying the efficacy of first aid treatments for burn injuries using mathematical modelling and in vivo porcine experiments

10.1101/131391 ◽

2017 ◽

Author(s):

Matthew J Simpson ◽

Sean McInerney ◽

Elliot J Carr ◽

Leila Cuttle

Keyword(s):

Experimental Data ◽

Mathematical Model ◽

Thermal Energy ◽

Tissue Damage ◽

Burn Injury ◽

Blood Perfusion ◽

First Aid ◽

Burn Injuries ◽

Threshold Temperature

AbstractFirst aid treatment of burn injuries reduces scarring and improves healing. Here, we quantify the efficacy of various first aid treatments by using a mathematical model to describe a suite of experimental data from a series of in vivo porcine experiments. We study a series of consistent burn injuries that are subject to first aid treatments that vary in both the temperature and duration of the first aid treatment. Calibrating the mathematical model to the experimental data provides estimates of the in vivo thermal diffusivity, the rate at which thermal energy is lost to the blood (perfusion), and the heat transfer coefficient controlling the loss of thermal energy at the interface of the fat and muscle layers. A limitation of working with in vivo animal experiments is the difficulty of resolving spatial variations in temperature across the tissues. Here, we use the solution of the calibrated mathematical model to predict and visualise the temperature distribution across the thickness of the tissue during the creation of the burn injury and the application of various first aid treatments. Using this information we propose, and report values for, a novel measure of the potential for tissue damage. This measure quantifies two important aspects that are thought to be related to thermal injury: (i) the volume of tissue that rises above the threshold temperature associated with the accumulation of tissue damage; and, (ii) the duration of time that the tissue remains above this threshold temperature. We conclude by discussing the clinical relevance of our findings.

Download Full-text

Indole Treatment Alleviates Intestinal Tissue Damage Induced by Chicken Coccidiosis Through Activation of the Aryl Hydrocarbon Receptor

Frontiers in Immunology ◽

10.3389/fimmu.2019.00560 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 5

Author(s):

Woo H. Kim ◽

Hyun S. Lillehoj ◽

Wongi Min

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Tissue Damage ◽

Intestinal Tissue ◽

Aryl Hydrocarbon

Download Full-text

Alcohol Intoxication and the Postburn Gastrointestinal Hormonal Response

Journal of Burn Care & Research ◽

10.1093/jbcr/irz083 ◽

2019 ◽

Vol 40 (6) ◽

pp. 785-791 ◽

Cited By ~ 1

Author(s):

Juan-Pablo Idrovo ◽

Jill A Shults ◽

Brenda J Curtis ◽

Michael M Chen ◽

Elizabeth J Kovacs

Keyword(s):

Burn Injury ◽

Alcohol Intoxication ◽

Hormone Secretion ◽

Gastrointestinal Hormones ◽

Gastric Inhibitory Polypeptide ◽

Serum Levels ◽

Gastrointestinal Hormone ◽

Hormonal Changes ◽

Ethanol Intoxication ◽

Burn Victims

Abstract Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.

Download Full-text