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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Ethanol-mediated dysregulation of cytokines and human anti-microbial peptide cathelicidin

January 2020 (has links)
archives@tulane.edu / Ethanol consumption is known to increase the prevalence and severity of respiratory infection and impaired immunity. The relationships between ethanol exposure, vitamin D levels, the anti-microbial protein cathelicidin/LL-37, other chemokines and cytokines, and their roles in pulmonary infections are explored in this report. Information from experimental model systems that included pulmonary cell culture, mice, and primates were compared to data from humans with alcohol use disorder (AUD) and normal controls. Cathelicidin/LL-37 levels were reduced by ethanol exposure of Nuli-1 airway epithelial cells, which is consistent with the model of enhanced airway sensitivity to infection. The vitamin D receptor positively regulates cathelicidin/LL-37 levels. A reduction in the circulating vitamin D in the Rhesus monkey model following ethanol exposure that may impact cathelicidin/LL-37 expression. Serum samples from ethanol exposed mice, Rhesus monkeys and humans with AUD showed variable expression patterns with respect to cytokines and chemokine, some of which may relate to changes in immunity and infection sensitivity. Protein microarrays revealed altered inflammatory biomarkers in the ethanol-exposed population with AUD. Principle component analysis-derived clustering methodology signaled the presence of systemic inflammation in AUD subjects. The combination of immunological impairment and persistent inflammatory biomarkers are consistent with the known predisposition of individuals with AUD to the development of respiratory infections and acute respiratory distress syndrome. / 1 / Phanuwat Sriyotha
2

Protective Mechanical Ventilation in Inflammatory and Ventilator-Associated Pneumonia Models

Sperber, Jesper January 2016 (has links)
Severe infections, trauma or major surgery can each cause a state of systemic inflammation. These causes for systemic inflammation often coexist and complicate each other. Mechanical ventilation is commonly used during major surgical procedures and when respiratory functions are failing in the intensive care setting. Although necessary, the use of mechanical ventilation can cause injury to the lungs and other organs especially under states of systemic inflammation. Moreover, a course of mechanical ventilator therapy can be complicated by ventilator-associated pneumonia, a factor greatly influencing mortality. The efforts to avoid additional ventilator-induced injury to patients are embodied in the expression ‘protective ventilation’. With the use of pig models we have examined the impact of protective ventilation on systemic inflammation, on organ-specific inflammation and on bacterial growth during pneumonia. Additionally, with a 30-hour ventilator-associated pneumonia model we examined the influence of mechanical ventilation and systemic inflammation on bacterial growth. Systemic inflammation was initiated with surgery and enhanced with endotoxin. The bacterium used was Pseudomonas aeruginosa. We found that protective ventilation during systemic inflammation attenuated the systemic inflammatory cytokine responses and reduced secondary organ damage. Moreover, the attenuated inflammatory responses were seen on the organ specific level, most clearly as reduced counts of inflammatory cytokines from the liver. Protective ventilation entailed lower bacterial counts in lung tissue after 6 hours of pneumonia. Mechanical ventilation for 24 h, before a bacterial challenge into the lungs, increased bacterial counts in lung tissue after 6 h. The addition of systemic inflammation by endotoxin during 24 h increased the bacterial counts even more. For comparison, these experiments used control groups with clinically common ventilator settings. Summarily, these results support the use of protective ventilation as a means to reduce systemic inflammation and organ injury, and to optimize bacterial clearance in states of systemic inflammation and pneumonia.
3

The effects of high intensity interval training on resting mean arterial pressure and C-reactive protein content in prehypertensive subjects

Skutnik, Benjamin C. January 1900 (has links)
Master of Science / Department of Kinesiology / Craig A. Harms / Subjects with prehypertension are at risk for developing hypertension (HTN). Hypertension is associated with low-grade systemic inflammation (LGSI). Aerobic exercise training (ET) is a proven means to reduce both blood pressure and LGSI in healthy and diseased subjects. Recently, high intensity interval training (HIIT) has been show to elicit similar cardiovascular and metabolic adaptations as ET in healthy and at-risk populations in a more time efficient manner. Therefore, we hypothesized that HIIT would elicit greater reductions in blood pressure and LGSI than ET. Twelve pre-hypertensive subjects (systolic blood pressure 127.0 ± 8.5 mmHg; diastolic blood pressure 86.2 ± 4.1 mmHg) were randomly assigned to an ET group (n=5) and a HIIT group (n=7). All subjects performed an incremental test to exhaustion (VO2max) on a cycle ergometer prior to, after 4 weeks, and after 8 weeks of training. Resting heart rate and blood pressure were measured prior to and three times a week during training. LGSI was measured via high-sensitivity C-reactive protein (hs-CRP) prior to, after 4 weeks and after 8 weeks of training. ET subjects performed an eight week exercise training program at 40% VO2 reserve determined from the VO2max test, while HIIT subjects performed exercise at 60% peak power determined from the VO2max test. ET group trained four days/week while HIIT trained three days/week. ET exercised for 30 minutes continuously at a constant workload and cadence of 60 rpm while HIIT performed a protocol on a 1:1 work-to-rest ratio at a constant workload and cadence of 100 rpm. Both groups showed similar (p<0.05) decreases in mean arterial (ET = -7.3%, HIIT = -4.5%), systolic (ET = -6.6%, HIIT = -8.8%), and diastolic (ET= -9.7, HIIT= -8.2%) blood pressure. HIIT decreased in LGSI (-33.7%) while ET did not change LGSI (p>0.05). VO2max increased ~25% with both HIIT and ET with no differences (p>0.05) between groups. These data suggest both HIIT and ET similarly decreased resting blood pressure and increased VO2max while HIIT was effective in decreasing LGSI in subjects who were pre-hypertensive.
4

Marcadores inflamatórios locais e sistêmicos em tabagistas com e sem doença pulmonar obstrutiva crônica /

Pelegrino, Nilva Regina Gelamo. January 2009 (has links)
Orientador: Irma de Godoy / Banca: José Antonio Baddini Martinez / Banca: Maria do Patrocínio Tenório Nunes / Banca: Aparecida Yooko Outa Angeleli / Banca: Alexandrina Sartori / Resumo: A doença pulmonar obstrutiva crônica (DPOC) está associada a processo inflamatório; entretanto, a definição de quais marcadores participam do processo inflamatório local e sistêmico, e suas correlações com o tabagismo e com a intensidade de obstrução das vias aéreas, ainda não está esclarecida. Avaliar simultaneamente a inflamação no sangue periférico e nas vias aéreas de tabagistas com e sem DPOC e avaliar a associação com o estado de tabagismo atual e com a gravidade da doença. Foram avaliados 52 pacientes com DPOC moderada a muito grave com idade média de 63,6±8,9 anos e VEF1(%) 50,6±17,1 e 20 indivíduos tabagistas com idade média de 49,1±6,2 anos e VEF1(%) 106,5±15,8. Todos os indivíduos da pesquisa foram submetidos à avaliação clínica, espirometria pré e pós-broncodilatador, oximetria de pulso, avaliação nutricional, teste de caminhada de seis minutos (TC-6), indução e coleta de escarro e coleta de sangue para exames bioquímicos e dosagem dos seguintes mediadores inflamatórios: TNF-a, IL-6, IL-8, IL-10 e PCR. Os tabagistas sem obstrução das vias aéreas apresentaram maiores níveis séricos de TNF-a quando comparados aos pacientes com DPOC. Além disso, entre os pacientes com DPOC, aqueles que eram tabagistas ativos apresentaram elevação da concentração sérica de TNF-a em relação aos ex-tabagistas. A IL-6 e a PCR estavam elevadas nos pacientes com DPOC comparados aos tabagistas sem obstrução das vias aéreas. No escarro induzido os pacientes com DPOC apresentaram maiores níveis do TNF-a e da IL-10 em relação aos tabagistas. Em relação à gravidade da doença, houve aumento do TNF-a sérico nos pacientes com doença moderada em relação aos com DPOC grave ou muito grave, e elevação do TNF-a e da IL-10 no escarro induzido dos pacientes ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chronic obstructive pulmonary disease ( COPD) is an inflammatory disease; however, the markers that characterize the localized and systemic inflammation and the... (Complete abstract click electronic access below) / Doutor
5

Efeito do MK-886 sobre a produção de leucotrienos e citocinas em animais sépticos / Effect of MK-886 in leukotrienes and cytokines production in septic animals

Pereira, Juliana Borges 10 February 2012 (has links)
Os leucotrienos (LTs) e as citocinas são mediadores inflamatórios produzidos durante a sepse e que podem apresentar uma tarefa moduladora na secreção de arginina-vasopressina (AVP). Na fase aguda da sepse as concentrações plasmáticas de AVP encontram-se aumentadas e na fase tardia em níveis basais, apesar da hipotensão progressiva. Nosso objetivo foi analisar o efeito da injeção intraperitoneal de MK-886, (inibidor da síntese de leucotrienos), sobre a produção de LTs e de citocinas no sítio infeccioso e plasma de animais sépticos. Foram usados ratos Wistar que receberam injeções intraperitoneais de MK-886 (4mg/kg) ou veículo (DMSO 5%) 1h antes da indução de sepse experimental por ligadura e perfuração cecal (CLP) ou da operação fictícia (OF). Os animais foram decapitados 0, 4 e 24h após CLP ou OF. O sangue foi coletado para a determinação do sódio sérico, hematócrito, citocinas, LTB4. O lavado peritoneal foi coletado para dosagem de citocinas. O hipotálamo foi removido e incubado para a análise de cis-LTs. O sódio sérico diminuiu, o hematócrito aumentou e os cis-leucotrienos hipotalâmicos não apresentaram alterações significantes após 4 horas de CLP. A sepse provocou um aumento nas concentrações de TNF-a, no sítio infeccioso, mas não foi detectada no plasma. As citocinas IL-1b e a IL-6 aumentaram em 4 horas tanto no sítio infeccioso como no plasma. A análise dos resultados de LTB4 plasmático mostrou uma diminuição das concentrações 24 horas após o CLP. A administração do MK-886 não modificou o sódio, o hematócrito e aparentemente nem os cis-leucotrienos hipotalâmicos. No sítio infeccioso a droga causou um aumento nas concentrações de TNF-a 4 e 24 horas enquanto as de IL-1b não se modificaram e as de IL-6 aumentaram apenas 4 horas após o CLP. Entretanto, no plasma, a droga diminuiu acentuadamente as concentrações tanto de IL-1b como de IL-6. A análise do LTB4 plasmático mostrou efeito da droga em 4 horas, mas não em 24 horas da sepse. Os resultados deste estudo sugerem que os LTS regulam de maneira diferente a produção de citocinas no plasma e no foco infeccioso e podem explicar os efeitos destes mediadores sobre a secreção de AVP durante a sepse. / Leukotrienes (LTs) and cytokines are inflammatory mediators produced during sepsis and may have a task in modulating the secretion of vasopressin (VP). In the acute phase of sepsis, the plasma AVP concentrations are increased and in the late stage at basal levels, despite the progressive hypotension. Our goal was to analyze the effect of intraperitoneal injection of MK-886 (leukotriene synthesis inhibitor) on the production of LTs and cytokines in the infectious site and plasma of septic animals. We used Wistar rats that received intraperitoneal injection of MK-886 (4.0mg/kg) or vehicle (DMSO 5%) 1 h before induction of experimental sepsis by cecal ligation and puncture (CLP) or sham operation (OF).The animals were decapitated at 0, 4 and 24 h after surgeries and blood was collected for determination of serum sodium, hematocrit, cytokines and LTB4. The peritoneal fluid was collected for cytokine assay. The hypothalamus was removed and incubated for the analysis of cis-LTs. Serum sodium decreased, hematocrit increased and hypothalamic cis-leukotrienes did not show significant changes after 4 hours of CLP. Sepsis caused increase in the TNF-a concentrations in the site of infection, but was not detected in plasma. The cytokines IL-1b and IL-6 increased by 4 hours both in the plasma as in the site of infection. The results of LTB4 showed a decrease in plasma concentrations 24 hours after CLP. The administration of MK-886 did not alter sodium, hematocrit, and apparently neither the cis-hypothalamic leukotrienes. At the site of infection the drug caused an increase in the concentrations of TNF-a 4 and 24 hours while IL-1b remained unchanged and IL-6 increased only 4 hours after CLP. However, in the plasma the drug markedly diminished the concentrations of IL-1b and IL-6. The analysis of LTB4 in plasma showed effects of the drug in 4 hours but not 24 hours of sepsis. The results of this study suggest that LTs differentially regulate the cytokine production in the plasma and in the site of infection, and may explain the effects of these mediators in AVP secretion during sepsis.
6

Marcadores inflamatórios locais e sistêmicos em tabagistas com e sem doença pulmonar obstrutiva crônica

Pelegrino, Nilva Regina Gelamo [UNESP] 12 February 2009 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:32:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-12Bitstream added on 2014-06-13T19:02:38Z : No. of bitstreams: 1 pelegrino_nrg_dr_botfm.pdf: 438903 bytes, checksum: 09acfacac5e9ede2ba3677fb88fa0cee (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A doença pulmonar obstrutiva crônica (DPOC) está associada a processo inflamatório; entretanto, a definição de quais marcadores participam do processo inflamatório local e sistêmico, e suas correlações com o tabagismo e com a intensidade de obstrução das vias aéreas, ainda não está esclarecida. Avaliar simultaneamente a inflamação no sangue periférico e nas vias aéreas de tabagistas com e sem DPOC e avaliar a associação com o estado de tabagismo atual e com a gravidade da doença. Foram avaliados 52 pacientes com DPOC moderada a muito grave com idade média de 63,6±8,9 anos e VEF1(%) 50,6±17,1 e 20 indivíduos tabagistas com idade média de 49,1±6,2 anos e VEF1(%) 106,5±15,8. Todos os indivíduos da pesquisa foram submetidos à avaliação clínica, espirometria pré e pós-broncodilatador, oximetria de pulso, avaliação nutricional, teste de caminhada de seis minutos (TC-6), indução e coleta de escarro e coleta de sangue para exames bioquímicos e dosagem dos seguintes mediadores inflamatórios: TNF-a, IL-6, IL-8, IL-10 e PCR. Os tabagistas sem obstrução das vias aéreas apresentaram maiores níveis séricos de TNF-a quando comparados aos pacientes com DPOC. Além disso, entre os pacientes com DPOC, aqueles que eram tabagistas ativos apresentaram elevação da concentração sérica de TNF-a em relação aos ex-tabagistas. A IL-6 e a PCR estavam elevadas nos pacientes com DPOC comparados aos tabagistas sem obstrução das vias aéreas. No escarro induzido os pacientes com DPOC apresentaram maiores níveis do TNF-a e da IL-10 em relação aos tabagistas. Em relação à gravidade da doença, houve aumento do TNF-a sérico nos pacientes com doença moderada em relação aos com DPOC grave ou muito grave, e elevação do TNF-a e da IL-10 no escarro induzido dos pacientes... / Chronic obstructive pulmonary disease ( COPD) is an inflammatory disease; however, the markers that characterize the localized and systemic inflammation and the... (Complete abstract click electronic access below)
7

Efeito do MK-886 sobre a produção de leucotrienos e citocinas em animais sépticos / Effect of MK-886 in leukotrienes and cytokines production in septic animals

Juliana Borges Pereira 10 February 2012 (has links)
Os leucotrienos (LTs) e as citocinas são mediadores inflamatórios produzidos durante a sepse e que podem apresentar uma tarefa moduladora na secreção de arginina-vasopressina (AVP). Na fase aguda da sepse as concentrações plasmáticas de AVP encontram-se aumentadas e na fase tardia em níveis basais, apesar da hipotensão progressiva. Nosso objetivo foi analisar o efeito da injeção intraperitoneal de MK-886, (inibidor da síntese de leucotrienos), sobre a produção de LTs e de citocinas no sítio infeccioso e plasma de animais sépticos. Foram usados ratos Wistar que receberam injeções intraperitoneais de MK-886 (4mg/kg) ou veículo (DMSO 5%) 1h antes da indução de sepse experimental por ligadura e perfuração cecal (CLP) ou da operação fictícia (OF). Os animais foram decapitados 0, 4 e 24h após CLP ou OF. O sangue foi coletado para a determinação do sódio sérico, hematócrito, citocinas, LTB4. O lavado peritoneal foi coletado para dosagem de citocinas. O hipotálamo foi removido e incubado para a análise de cis-LTs. O sódio sérico diminuiu, o hematócrito aumentou e os cis-leucotrienos hipotalâmicos não apresentaram alterações significantes após 4 horas de CLP. A sepse provocou um aumento nas concentrações de TNF-a, no sítio infeccioso, mas não foi detectada no plasma. As citocinas IL-1b e a IL-6 aumentaram em 4 horas tanto no sítio infeccioso como no plasma. A análise dos resultados de LTB4 plasmático mostrou uma diminuição das concentrações 24 horas após o CLP. A administração do MK-886 não modificou o sódio, o hematócrito e aparentemente nem os cis-leucotrienos hipotalâmicos. No sítio infeccioso a droga causou um aumento nas concentrações de TNF-a 4 e 24 horas enquanto as de IL-1b não se modificaram e as de IL-6 aumentaram apenas 4 horas após o CLP. Entretanto, no plasma, a droga diminuiu acentuadamente as concentrações tanto de IL-1b como de IL-6. A análise do LTB4 plasmático mostrou efeito da droga em 4 horas, mas não em 24 horas da sepse. Os resultados deste estudo sugerem que os LTS regulam de maneira diferente a produção de citocinas no plasma e no foco infeccioso e podem explicar os efeitos destes mediadores sobre a secreção de AVP durante a sepse. / Leukotrienes (LTs) and cytokines are inflammatory mediators produced during sepsis and may have a task in modulating the secretion of vasopressin (VP). In the acute phase of sepsis, the plasma AVP concentrations are increased and in the late stage at basal levels, despite the progressive hypotension. Our goal was to analyze the effect of intraperitoneal injection of MK-886 (leukotriene synthesis inhibitor) on the production of LTs and cytokines in the infectious site and plasma of septic animals. We used Wistar rats that received intraperitoneal injection of MK-886 (4.0mg/kg) or vehicle (DMSO 5%) 1 h before induction of experimental sepsis by cecal ligation and puncture (CLP) or sham operation (OF).The animals were decapitated at 0, 4 and 24 h after surgeries and blood was collected for determination of serum sodium, hematocrit, cytokines and LTB4. The peritoneal fluid was collected for cytokine assay. The hypothalamus was removed and incubated for the analysis of cis-LTs. Serum sodium decreased, hematocrit increased and hypothalamic cis-leukotrienes did not show significant changes after 4 hours of CLP. Sepsis caused increase in the TNF-a concentrations in the site of infection, but was not detected in plasma. The cytokines IL-1b and IL-6 increased by 4 hours both in the plasma as in the site of infection. The results of LTB4 showed a decrease in plasma concentrations 24 hours after CLP. The administration of MK-886 did not alter sodium, hematocrit, and apparently neither the cis-hypothalamic leukotrienes. At the site of infection the drug caused an increase in the concentrations of TNF-a 4 and 24 hours while IL-1b remained unchanged and IL-6 increased only 4 hours after CLP. However, in the plasma the drug markedly diminished the concentrations of IL-1b and IL-6. The analysis of LTB4 in plasma showed effects of the drug in 4 hours but not 24 hours of sepsis. The results of this study suggest that LTs differentially regulate the cytokine production in the plasma and in the site of infection, and may explain the effects of these mediators in AVP secretion during sepsis.
8

The systemic inflammatory response to dental plaque

Wahaidi, Vivian Y. January 2010 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: Bacteremia involving oral bacteria and the systemic inflammatory responses are mechanisms that could causally link oral and systemic diseases. Objective: To use an experimental gingivitis model (EGM) in 2 clinical studies to 1) examine the systemic inflammatory responses to dental plaque, and assess racial differences in these responses; 2) determine whether dental plaque accumulation causes bacteremia and subsequent systemic responses following toothbrushing. Additionally, a laboratory study was conducted to examine the interaction between circulating human neutrophils and Fusobacterium nucleatum. Methods: For both clinical studies, healthy adults, aged 18-31 years, were recruited. In the first study, black and white, males and females participated in a 21-day EGM; in the second study, white adults participated in a 7-day EGM. In both studies, subjects visited the clinic weekly for: 1) measurement of the plaque index (PI) and gingival index (GI); 2) collection of peripheral blood samples to evaluate systemic markers of inflammation. In the second study, to analyze bacteremic episodes during the experimental phase, peripheral blood samples were collected at baseline and at 0.5, 5, and 30 minutes post-toothbrushing. In the laboratory study, interactions between F. nucleatum and circulating neutrophils were examined using a luminol-enhanced chemiluminescence assay. Results: During the experimental phases of both clinical studies, PI and GI increased (p<0.05) with a correlation between PI and GI ≥0.79. In the first study, dental plaque accumulation resulted in a systemic response that manifested as changes (p<0.05) in the level of inflammatory markers, hematologic factors, markers of lipid metabolism, and markers of metabolic change. This systemic response differed between individuals of different gender and race. In the second study, bacteremic episodes and changes in hematologic factors were observed post-toothbrushing during the experimental phase. Activation of neutrophils with F. nucleatum, in the laboratory study, increased the levels of neutrophil chemiluminescence (p<0.05). Conclusions: Overall, the findings of these investigations may shed light on the mechanistic pathways by which oral infection may impose risk for systemic diseases and provide some evidence to support a possible causal association between oral and systemic diseases. The clinical significance of this in systemic inflammatory diseases requires further investigation.
9

The Effects of Flaxseed and Flaxseed Oil on the Gut-Brain Axis in Lipopolysaccharide-Challenged Male C57Bl/6 Mice

Livingston, Dawson 15 September 2022 (has links)
Individuals living with depression and anxiety show systemic increases of the bacterial endotoxin lipopolysaccharide (LPS), which induces an inflammatory cascade, resulting in negative effects across the gut-brain axis (GBA). LPS administration in mice has previously been used as a rodent model of depression/anxiety. Flaxseed (FS) contains key bioactives, including an omega-3 fatty-acid, dietary fibre, and a poly-phenolic compound which all may attenuate the effects of LPS through modulation of the GBA. The objectives of this thesis were to examine the effects of LPS on the GBA in C57Bl/6 mice and to determine if dietary supplementation with FS and/or FS oil (FO) provided protection against the LPS challenge. The LPS-induced negative effects across the GBA were partially attenuated by dietary supplementation with FS, but not FO, through changes in microbiota composition/function and systemic-/neuro-inflammation. Therefore, the potential benefits of FS are independent of the oil or are synergistic of all bioactives.
10

NK cells and systemic inflammation : compartmentalization and memory responses / Cellules NK et inflammation systémique : compartimentalisation et réponse mémoire

Rasid, Orhan 08 November 2016 (has links)
L'inflammation systémique est une réaction qui implique l’ensemble de l’organisme suite une agression sévère, potentiellement mortelle, illustrée par le syndrome de réponse inflammatoire systémique (SIRS). De nombreux acteurs cellulaires et moléculaires contribuent au développement de cette cascade inflammatoire parmi lesquels les cellules NK jouent un rôle clé. Malgré l'accumulation de preuves sur l’existence de propriétés spécifiques à chaque organe en réponse à l'inflammation systémique, en termes de cellules NK, on sait peu de choses sur la dynamique compartimentalisée de l’activation des cellules NK pendant un SIRS. En outre, le statut immunitaire des cellules NK après la résolution d’un SIRS est également mal connu. Dans le présent travail, nous avons étudié les réponses des cellules NK provenant de différents organes en utilisant un modèle d’endotoxinémie murine. Nous avons caractérisé la réponse des cellules NK au sein de la rate, du poumon, de la moelle osseuse, de la cavité péritonéale, et dans la circulation. Nous avons trouvé que, malgré une dynamique similaire de la réponse dans les différents organes, les réponses des cellules NK sont compartimentalisées avec des seuils différent et spécifiques. A l’aide de transferts adoptifs, nous avons constaté que la réactivité des cellules NK spécifiques d'organes peut refléter le compartiment d’origine lors des phases initiales de l'inflammation. Cependant, les cellules NK ont la capacité de s’adapter rapidement à leur nouvel environnement et d'ajuster leurs niveaux de réponse à ceux des cellules NK résidentes. Ainsi, cette étude fournit une preuve de concept qui confirme la compartimentalisation de la réponse des cellules NK lors de l'inflammation systémique. Dans une deuxième partie, nous avons analysé le statut des cellules NK à différents moments après une endotoxinémie. Les réponses des cellules NK au sein d’une préparation de cellules de la rate sont fortement supprimées en réponse à une restimulation in vitro, 14 jours après l'endotoxinémie. Cependant, nous avons montré que la réactivité intrinsèque des cellules NK est en fait augmentée après l'injection d’endotoxine, aboutissant à des cellules NK présentant des caractéristiques de cellules NK mémoires. Des expériences de transfert adoptif ont confirmé les propriétés de mémoire des cellules NK après endotoxinémie. Nos résultats accroissent la connaissance concernant le rôle des cellules NK dans un contexte d'inflammation systémique, révélant des réponses compartimentalisés et l’induction d’une mémoire suite à l’endotoxinémie. L'observation selon laquelle les cellules NK développent des propriétés de mémoire après une inflammation systémique dans le contexte d'un environnement suppressif est d’une grande nouveauté et ce phénomène est rapporté pour la première fois. / Systemic inflammation is whole-body reaction to a triggering insult that often results in life threatening illness like systemic inflammatory response syndrome (SIRS). Contributing to the development of this inflammatory cascade are numerous cellular and molecular players, among which, NK cells have been shown to play a key role. Despite accumulating evidence on the organ-specific properties of both systemic inflammation and NK cells, little is known about the compartmentalized dynamics of NK cell activation during SIRS. Furthermore, the status of NK cells after the resolution of SIRS is also poorly characterized. In the present work, we investigated NK responses in different organs using a mouse model of endotoxinemia and characterized the compartmentalized response of spleen, lung, bone marrow, peritoneal and circulating NK cells. We found that despite similar dynamics of response in different organs, NK cells responses, are compartmentalized with seemingly specific thresholds of maximum activation. Using a series of adoptive transfers, we found that while organ-specific NK cell responsiveness can affect the initial phases of inflammation, these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. Thus, this study provides proof of concept data on the compartmentalization of the NK cell responses during systemic inflammation. In a second part, we assessed the status of NK cells at different times after endotoxemia. NK cells responses in the context of whole spleen preparations were severely suppressed in response to in vitro restimulation at 14 days after endotoxemia. However, intrinsic NK cell responsiveness was increased after endotoxemia, showing characteristics of NK cell memory. Adoptive transfer experiments confirmed memory properties of NK cells after endotoxemia. Overall, these results expand on the role of NK cells in the context of systemic inflammation revealing compartmentalized responses during and memory properties following endotoxemia. The observation that NK cells develop memory properties after systemic inflammation in the context of a suppressive environment is of the highest novelty and the first one to report such a phenomenon.

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