Trauma-Induced Damage-Associated Molecular Patterns-Mediated Remote Organ Injury and Immunosuppression in the Acutely Ill Patient

Trauma is one of the leading causes of death and disability in the world. Multiple trauma or isolated traumatic brain injury are both indicative of human tissue damage. In the early phase after trauma, damage-associated molecular patterns (DAMPs) are released and give rise to sterile systemic inflammatory response syndrome (SIRS) and organ failure. Later, protracted inflammation following sepsis will favor hospital-acquired infection and will worsen patient’s outcome through immunosuppression. Throughout medical care or surgical procedures, severe trauma patients will be subjected to endogenous or exogenous DAMPs. In this review, we summarize the current knowledge regarding DAMP-mediated SIRS or immunosuppression and the clinical consequences in terms of organ failure and infections

Trauma-Induced Damage-Associated Molecular Patterns-Mediated Remote Organ Injury and Immunosuppression in the Acutely Ill Patient

International audienc

presentation_1_Trauma-Induced Damage-Associated Molecular Patterns-Mediated Remote Organ Injury and Immunosuppression in the Acutely Ill Patient.PDF

<p>Trauma is one of the leading causes of death and disability in the world. Multiple trauma or isolated traumatic brain injury are both indicative of human tissue damage. In the early phase after trauma, damage-associated molecular patterns (DAMPs) are released and give rise to sterile systemic inflammatory response syndrome (SIRS) and organ failure. Later, protracted inflammation following sepsis will favor hospital-acquired infection and will worsen patient’s outcome through immunosuppression. Throughout medical care or surgical procedures, severe trauma patients will be subjected to endogenous or exogenous DAMPs. In this review, we summarize the current knowledge regarding DAMP-mediated SIRS or immunosuppression and the clinical consequences in terms of organ failure and infections.</p

Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells

Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-γ in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-γ after IL-12 priming. The modulation of IFN-γ production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates IFN-γ production and control ERK activation. In vivo, ExoT also increases IFN-γ levels and the percentage of IFN-γ+ NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-γ by NK cells after PA infection through ERK activation

Baclofen to Prevent Agitation in Alcohol-Addicted Patients in the ICU: Study Protocol for a Randomised Controlled Trial

International audienceBACKGROUND: Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30~% and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50~% of patients. METHODS/DESIGN: This prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28~days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal~(such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway~(leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment. DISCUSSION: Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016

Nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial

International audienc

Interleukin-22 regulates interferon lambda expression in a mice model of pseudomonas aeruginosa pneumonia

International audienceBackground:Interleukin (IL)-22 is a cytokine involved in tissue protection and repair following lung pathologies.Interferon (IFN)-λcytokines displayed similar properties during viral infection and a synergy of action betweenthese two players has been documented in the intestine. We hypothesize that duringPseudomonas aeruginosachallenge, IL-22 up-regulates IFN-λand that IFN-λexhibits protective functions duringPseudomonas aeruginosaacute pneumonia model in mice.Methods:Using an in vitro human alveolar epithelial cell line A549, we assessed the ability of IL-22 to enhanceIFN-λexpression during infection. IFN-λprotective function was evaluated in an acute mouse pneumonia model.Results:Wefirst demonstrated in murine lungs that only type-II alveolar cells express IL-22 receptor and that IL-22 treatment of A549 cell line up-regulates IFN-λexpression. In a murine acute pneumonia model, IL-22 ad-ministration maintained significant IFN-λlevels in the broncho-alveolarfluids whereas IL-22 neutralizationabolished IFN-λup-regulation. In vivo administration of IFN-λduringPseudomonas aeruginosapneumonia im-proves mice outcome by dampening neutrophil recruitment and decreasing epithelium damages.Discussion:We show here that IL-22 regulates IFN-λlevels duringPseudomonas aeruginosapneumonia

Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells

International audiencePseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-γ in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-γ after IL-12 priming. The modulation of IFN-γ production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates IFN-γ production and control ERK activation. In vivo, ExoT also increases IFN-γ levels and the percentage of IFN-γ[+] NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-γ by NK cells after PA infection through ERK activation

Hydrocortisone Prevents Immunosuppression by Interleukin-10+ Natural Killer Cells After Trauma-Hemorrhage

Hydrocortisone Prevents Immunosuppression by Interleukin-10+ Natural Killer Cells After Trauma-Hemorrhag