201 |
Análise da coinfecção entre ureaplasmas e o vírus do Papiloma Humano (HPV) em amostras cervicais e em um modelo de estudo \"in vitro\" de queratinócitos primários humanos (PHK). / Analysis of co-infection among ureaplasmas and the Human Papilloma Vírus (HPV) in cervical samples and in a infection model in vitro in primary human keratinocytes (PHK).Aline Teixeira Amorim 30 April 2015 (has links)
O desenvolvimento do câncer cervical depende da exposição ao HPV, fator necessário, mas não suficiente. Outras bactérias, tais como ureaplasmas, têm sido associadas como cofatores. O objetivo deste estudo foi avaliar a presença de ureaplasmas em mulheres com lesão cervical, e observar alterações em PHK causadas pela infecção por ureaplasmas. 140 swabs vaginais foram coletados. O material foi submetido a PCR para a detecção de HPV, Mollicutes, U. urealyticum, U. parvum e seus sorotipos, e outras bactérias de importância ginecológica; e qPCR para U. urealyticum e U. parvum. Também foi realizada a infecção de ureaplasmas em PHK transformados com HPV. As células foram contadas e realizou-se a dosagem das citocinas IL1-β, IL-6 e TNF-α. HPV, Mollicutes, U. parvum, sorotipos 1 e 6 de U. parvum, T. vaginalis e G. vaginalis, além de alguns fatores socioeconômicos, foram associados com lesão cervical. Verificou-se maior carga de U. parvum entre mulheres com lesão. Houve diminuição do número de células e maior liberação de IL-6 e TNF-α nos grupos infectados. Com os resultados obtidos neste estudo, foi possível verificar uma associação entre os ureaplasmas e HPV no início das lesões cervicais, contudo mais estudos precisam ser realizados para aprimorar essa hipótese. / The development of cervical cancer depends on the exposure to HPV, necessary factor, but not enough. Other bacteria, such as ureaplasmas, have been associated as cofactors. The aim of this study was to evaluate the presence of ureaplasmas in women with cervical injury, and observe changes in PHK infected by ureaplasmas. 140 vaginal swabs were collected. The material was subjected to PCR for detection of HPV, Mollicutes, Ureaplasma urealyticum, U. parvum (and serotypes) and other bacteria gynecological importance; qPCR for U. urealyticum and U. parvum was made. PHK transformed by HPV was infected by ureaplasma. Cells were counted and it was done titration of IL1-β, IL-6 and TNF-α. HPV, Mollicutes, U. parvum, serotypes 1 and 6 U. parvum, T. vaginalis and G. vaginalis, and some socioeconomic factors were associated with cervical injury. Besides this, it was detected higher load U. parvum among women with injury. There was decrease in cell number and increased release of IL-6 and TNF-α in infected groups. With the results of this study, we found an association among HPV and ureaplasmas at the beginning of cervical lesions, but more studies are needed to enhance this hypothesis.
|
202 |
Modulation de l'expression des CYP1A2 et CYP3A6 par l'interleukine-1B[beta] et l'interleukine-6Gabriac, Mélanie January 2007 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal
|
203 |
Μελέτη του ρυθμιστικού ρόλου του παράγοντα αναστολής της μετανάστευσης των μακροφάγων (MIF) στην επίδραση των κορτικοειδών στην παραγωγή μεταλλοπρωτεασών και των ενδογενών αναστολέων τους, κυτταροκινών και κολλαγόνου στο ρινικό πολύποδα / Study of the regulatory role of macrophage migration inhibitory factor (MIF) on the effect of corticosteroids on production of matrix metalloproteinases and their inhibitors (TIMPS), cytokines and collagen type-I in nasal polypsΣταθάς, Θεόδωρος 09 July 2013 (has links)
Στην παρούσα διατριβή μελετήθηκε η έκφραση του παράγοντα αναστολής της μετανάστευσης των μακροφάγων (MIF) στον ιστό από ρινικό πολύποδα αλλά και στον φυσιολογικό ρινικό βλεννογόνο, καθώς και η ικανότητα αυτού να εξουδετερώνει την ανασταλτική δράση των γλυκοκορτικοειδών (ΓΚ) στην επαγόμενη από διάφορους αυξητικούς παράγοντες παραγωγή διαμεσολαβητών, όπως η IL-6 η MMP-1, η MMP-3 το κολλαγόνο τύπου-Ι και ο TIMP-1, που εμπλέκονται στη παθογένεια του ρινικού πολύποδα (ΡΠ). Ο MIF ανιχνεύθηκε στο μέσο καλλιέργειας όλων των ιστών και σε όλα τα εκχυλίσματα. Η έκφρασή του ήταν αυξημένη στον ρινικό πολύποδα σε σχέση με τον φυσιολογικό ρινικό βλεννογόνο. O TGF-β1 προκάλεσε δοσο- και χρονο-εξαρτώμενη αύξηση των επιπέδων της IL-6 του TIMP-1 και του κολλαγόνου τύπου-Ι, και παράλληλα ο TNF-α προκάλεσε δοσο- αλλά και χρονο-εξαρτώμενη διέγερση στην παραγωγή της IL-6 του TIMP-1 και των μεταλλοπρωτεασών MMP-1 και MMP-3. Η δεξαμεθαζόνη προκάλεσε στατιστικά σημαντική και δοσοεξαρτώμενη μείωση της επαγόμενης από τον TGF-β1 και TNF-α, παραγωγής της IL-6 του TIMP-1 του κολλαγόνου τύπου-Ι και των μεταλλοπρωτεασών MMP-1 και MMP-3. Διερευνώντας τον μηχανισμό μέσω του οποίου η δεξαμεθαζόνη ασκεί την κατασταλτική της δράση στην επαγόμενη τόσο από τον TGF-β1 όσο και από τον TNF-α, παραγωγή της IL-6, φάνηκε πως αυτή εκδηλώνεται κυρίως μέσω της επαγωγής αλλά και της προστασίας της ΜΚΡ-1 και κατά συνέπεια της καταστολής του μονοπατιού των ΜΑΡΚ και της ενεργοποίησης του ΑΡ-1, και λιγότερο μέσω της καταστολής της ενεργοποίησης του NF-κB. Ο ISO-1, ένας αναστολέας της δράσης του MIF, ενίσχυσε σημαντικά την κατασταλτική επίδραση της δεξαμεθαζόνης στα επίπεδα της IL-6 και του TIMP-1 στο μέσο καλλιέργειας ιστού από ΡΠ, ενώ αντίθετα προκάλεσε αναστροφή της κατασταλτικής δράσης της δεξαμεθαζόνης, η οποία ήταν στατιστικά σημαντική για την ΜΜΡ-1 όχι όμως και για την ΜΜΡ-3. Η ενίσχυση της κατασταλτικής δράσης της δεξαμεθαζόνης παρουσία του ISO-1, που κυμάνθηκε από 15.0% έως 20.5% θα πρέπει μάλλον να οφείλεται στην αναστολή του ενδογενούς MIF από τον ISO-1. Συμπερασματικά, η παρουσία του MIF στον ιστό του ρινικού πολύποδα, φαίνεται να εξασθενίζει το κατασταλτικό αποτέλεσμα της δεξαμεθαζόνης στην παραγωγή IL-6 και TIMP-1 από αυτόν τον ιστό, ενώ η ταυτόχρονη χρήση του αναστολέα του MIF, ISO-1 οδηγεί σε μια περαιτέρω ενίσχυση της κατασταλτικής δράσης της δεξαμεθαζόνης. Έτσι, είναι λογικό κατ΄αρχήν, να προταθεί πως η δημιουργία ενός φαρμακευτικού σχήματος που περιέχει κορτιζόλη και ένα αναστολέα του MIF, θα μπορούσε να είναι πιο αποτελεσματικό στην θεραπεία της ΡΠ. Απαιτούνται περαιτέρω πειράματα με συνδυασμό ΓΚ και αναστολέων του MIF για να μελετηθεί η επίδρασή τους στη παραγωγή και άλλων παραγόντων που εμπλέκονται στη παθογένεια της ΡΠ προκειμένου να εξαχθούν ασφαλέστερα συμπεράσματα. / In the present study we investigated the expression of macrophage migration inhibitory factor (MIF) in nasal polyp tissues and also in normal nasal mucosa. The ability of MIF to neutralize the inhibitory effect of glucocorticoids on various growth factors induced expression of IL-6, TIMP-1, collagen type-I and matrix metalloproteinases MMP-1 and MMP-3, involved in the pathogenesis of nasal polyps, was studied. MIF was detected in all polyp tissue extracts and tissue culture conditioned media and its expression was increased in nasal polyps compared with normal nasal mucosa. TGF-b1 caused a dose-and time-dependent increase in levels of IL-6 of TIMP-1 and collagen type-I, while the TNF-a induced a dose-and time-dependent stimulation in the production of IL-6 of TIMP-1 and metalloproteinases MMP-1 and MMP-3. Dexamethasone caused a statistically significant and dose-dependent reduction induced by TGF-b1 and TNF-a, production of IL-6 of TIMP-1 of collagen type-I and the metalloproteinases MMP-1 and MMP-3. Investigating the mechanism by which dexamethasone exercises the suppressive action on both induced by TGF-b1 and by TNF-a, production of IL-6, showed that this occurs mainly through the induction and protection of MKP-1 and hence the suppression of the MAPK pathway and activation of AP-1, and less through the suppression of the activation of NF-kB. The ISO-1, an inhibitor of the action of MIF, significantly enhanced the suppressive effect of dexamethasone on the levels of IL-6 and TIMP-1 in tissue culture medium from nasal polyps. In contrary, ISO-1 induced inversion of the suppresive action of dexamethasone, which was statistically significant for MMP-1 but not for MMP-3. Enhancing of the suppresive action of dexamethasone in the presence of ISO-1, which ranged from 15.0% to 20.5% would probably be due to inhibition of endogenous MIF by ISO-1. In conclusion, the presence of MIF in nasal polyp tissue, appears to attenuate the suppressor effect of dexamethasone on the production of IL-6 and TIMP-1by this tissue, while simultaneously using the inhibitor of MIF, ISO-1 leads to an enhancement of dexamethasone activity. Therefore, it is reasonable to propose that the creation of a pharmaceutical regimen containing cortisol and an inhibitor of MIF, might be more effective in the treatment of nasal polyposis. Of course, requires further experiments with a combination of glucocorticoids and MIF inhibitors to study their effect on production of other factors involved in the pathogenesis of nasal polyposis in order to draw safer conclusions.
|
204 |
Strahleninduzierte Expression von pro-inflammatorischen Zytokinen nach selektiver Ganzleberbestrahlung in vivo (Ratte) / Radiation induced expression of pro-inflammatory cytokines after selective whole-liver irradiation in vivo (rat)Reuter, Felix 29 November 2017 (has links)
No description available.
|
205 |
Base moléculaire des effets de l'huile d'argan sur le métabolisme mitochondrial et peroxysomal des acides gras et sur l'inflammation / Molecular basis of the effects of argan oil on mitochondrial and peroxisomal metabolism of the fatty acids and inflammationEl Kebbaj, Riad 17 December 2012 (has links)
L’objectif des travaux de cette thèse a été d’explorer les bases moléculaires de l’effet de l’huile d’Argan (HA) sur le métabolisme lipidique au niveau mitochondriale et peroxysomale ainsi qu’élucider son potentiel anti-inflammatoire. Nous avons donc montré, dans un premier temps, que les méthodes artisanales préservaient les propriétés antioxydantes d’HA empêchant l’oxydation de l’acide férulique contrairement à l’HA d’origines commerciale. Ensuite, le traitement par l‘HA ou par les lipopolysaccharides (LPS) de fibroblastes humains, un modèle cellulaire de la pseudo-adrénoleucodystrophie néonatale (P-NALD), révèle pour l’HA une prolifération des peroxysomes indépendante de l’activation du récepteur nucléaire PPARα et de son coactivateur PGC-1α. Par contre, l’induction de la prolifération de peroxysomes par les LPS est accompagnée d’une activation de PPAR et de PGC-1Parallèlement, une étude a été réalisée au niveau hépatique chez des souris traitées par l‘HA ou par les LPS. Nous avons montré pour la première fois l’activité antioxydante de l’huile d’Argan in vivo au niveau hépatique par l’induction de l’activité enzymatique de la catalase peroxysomale et une activité hypolipémiante par la stimulation des activités déshydrogénases (ACADs) de la -oxydations mitochondriale des acides gars. De plus, l’HA induit la transcription des gènes PPECK et G6PH de la voie de la néoglucogenèse. Nous avons montré également pour la première fois un effet préventif de l’HA contre la répression des activités déshydrogénases des voies de -oxydations mitochondriale et peroxysomale, ainsi que celle la voie de la néoglucogenèse. Nos travaux démontrent que l’HA possède un potentiel anti-inflammatoire, induit par le LPS, élucidé par la répression de cytokines pro-inflammatoires IL-6 et TNFα et par l’induction de cytokines anti-inflammatoires IL10 et IL-4. L’ensemble de nos résultats indiquerait que l’huile d’Argan, du fait de sa composition riche en acide gras mono et polyinsaturés et en antioxydants, a des effets hypolipémiants et anti-inflammatoires au niveau hépatique qui se traduisent par une régulation de l’expression à la fois de récepteurs nucléaires et de leur gènes cibles ainsi que de certaines cytokines / The objective of this thesis work was to explore the molecular basis of Argan Oil (AO) effects on the mitochondrial and peroxisomal lipid metabolism and to elucidate its anti-inflammatory potential. We thus showed, initially, that the artisanal method preparation preserved the antioxidant properties of AO preventing the oxidation of the ferulic acid, by contrast to AO of commercial origin. Then, the treatment by the AO or lipopolysaccharides (LPS) of human fibroblasts, the cellular model of pseudo-neonatal adrenoleukodystrophy (P-NALD), revealed for the AO that peroxisomes proliferation is independent from the activation of the nuclear receptor PPARα and the co-activator PGC-1α. On the other side, the induction of the proliferation of peroxisomes by LPS is accompanied by an activation of both PPARα and PGC-1α. At the same time, mice treatments by AO or by the LPS showed, for the first time, the hepatic antioxidant activity of AO through the induction of the activity of the peroxisomal catalase. In addition, we showed a hypolipidemic activity of AO, by the stimulation of dehydrogenase activities (ACADs) of the mitochondrial fatty acid b-oxidation. Moreover, the AO induces the transcription of genes involved in gluconeogenesis pathway (i.e. PEPCK and G6PH). We also revealed, for the first time, the preventive effect of AO against LPS repressions of mitochondrial and peroxisomal fatty acid degradation as well as on the gluconeogenic pathway. Furthermore, the AO anti-inflammatory potential has been shown, in mice treated by LPS, through the repression of the pro-inflammatory cytokines IL-6 and TNFα and by the induction of the anti-inflammatory cytokines IL10 and IL-4. All together, our results may indicate that the Argan oil, because of its composition rich in mono and polyunsaturated fatty acids and in antioxidants as well, has a hypolipidemic and an anti-inflammatory effects, which are revealed by the regulation of the expressions of nuclear receptors and their target genes including several cytokines
|
206 |
Modulation de l'expression des CYP1A2 et CYP3A6 par l'interleukine-1B[beta] et l'interleukine-6Gabriac, Mélanie January 2007 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.
|
207 |
Rôle du TLR2 dans l’hépatite fulminante induite par le virus de l’hépatite murineBurnette, Mélanie 12 1900 (has links)
Ce travail examine les mécanismes de l’immunité innée impliqués dans l’hépatite aiguë virale du modèle murin d’infection par le virus de l’hépatite virale murine de type 3 (MHV-3). Afin de déterminer le rôle du TLR2 dans l’aggravation de l’hépatite, des infections avec le virus MHV-3 ont été réalisées in vivo chez des souris C57BL/6 et des souris déficientes pour le gène tlr2 et in vitro dans des macrophages et des hépatocytes infectés avec le virus MHV-3 et le virus moins virulent MHV-A59. Les niveaux de transcription et de traduction des senseurs microbiens, des interférons (IFN) de type I, des cytokines et/ou des chimiokines ont été évalués par qRT-PCR et ELISA. Les cellules ont été traitées avec des petits ARNs interférants (siRNAs) pour le TLR2 et le CEACAM1a ou mises en présence d’inhibiteurs des voies d’endocytose. Les résultats révèlent le rôle stimulateur du TLR2 pour la réplication virale, la production de cytokines pro-inflammatoires IL-6 et TNF-α et des chimiokines CXCL1, CXCL10 et CCL2. Un nouveau mécanisme d’échappement aux senseurs viraux dépendant du TLR2 a également été mis en évidence dans les macrophages et les hépatocytes lors de l’infection de ces cellules avec le virus MHV-3, et non pas avec le virus moins virulent MHV-A59. Ces différents travaux révèlent un nouveau rôle du TLR2 lors d’infections virales dans l'aggravation de la réponse inflammatoire tout en protégeant le virus des autres senseurs de la réponse immune innée. / This work investigates the innate immunity mechanisms involved in the Murine Hepatitis Virus type 3 (MHV-3) acute hepatitis disease model. In the goal of determining the role of the TLR2 receptor in aggravating the hepatitis disease, in vivo infections with the MHV-3 virus were performed on C57BL/6 mice or tlr2-/- gene knockout mice as well as in vitro infections of murine macrophages and hepatocytes with the MHV-3 and less virulent MHV-A59 serotypes. The levels of transcription and translation of different microbial sensors, type I interferons (IFN), cytokines and/or chemokines were measured by qRT-PCR and ELISA tests. Cells were treated with small interfering ARN (siRNA) for the TLR2 and/or CEACAM1a genes or treated with the different endocytosis inhibitors before infection. Our results reveal the stimulatory role of the TLR2 receptor on viral replication, production levels of the IL-6 and TNF-α cytokines and chemokines CXCL1, CXCL10 and CCL2. This study also reveals a new immune evasion mechanism via TLR2 in macrophages infected with MHV-3, but not with the lesser virulent MHV-A59 serotype. These different experiments have revealed a new role for the TLR2 receptor in viral infections wherein inflammatory responses are aggravated whilst shielding viral detection by other pathogens sensors of the innate immunity.
|
208 |
Syndrome inflammatoire chez les schizophrènes toxicomanesIgue, Raouf 12 1900 (has links)
La schizophrénie est une maladie mentale grave qui présente une comorbidité fréquente avec la toxicomanie et avec divers troubles immunitaires. Une méta-analyse réalisée récemment dans notre laboratoire a montré une augmentation d’IL-6 (une cytokine pro-inflammatoire), du récepteur soluble d’IL-2 (un marqueur d’activation du système immunitaire), et d’IL-1RA (une cytokine anti-inflammatoire) dans la schizophrénie, suggérant l’existence d’un syndrome inflammatoire dans cette maladie. La toxicomanie aussi est associée au dérèglement du réseau des cytokines inflammatoires, mais les effets dépendent du type de drogues et ils sont parfois diamétralement opposés. On dispose encore de peu d’informations sur le statut immunitaire et inflammatoire des patients qui ont un double diagnostic de schizophrénie et de toxicomanie. Le but de ce travail était d’explorer l’existence d’un état inflammatoire systémique chez les patients schizophrènes et toxicomanes, et l’influence du traitement avec un médicament antipsychotique atypique, la quétiapine. Les objectifs spécifiques étaient : 1) Mesurer les concentrations plasmatiques des cytokines inflammatoires chez les schizophrènes et toxicomanes avant, pendant et après traitement avec la quétiapine ; et 2) Faire des études de corrélations entre les taux de cytokines, les symptômes cliniques, et la consommation de drogues. Les résultats montrent que comparativement aux contrôles normaux, les patients avec un double diagnostic présentent une augmentation d’IL-6, d’IL-1RA, du sIL-2R et d’IL-8 avant traitement à la quétiapine. Les augmentations des concentrations plasmatiques d’IL-1RA sont particulièrement importantes chez les patients avec double diagnostic, si on les compare à celles publiées chez les schizophrènes sans toxicomanie. Le traitement à la quétiapine n’influence pas les concentrations plasmatiques de ces cytokines, sauf sIL-2R qui augmente davantage au cours du traitement. Des corrélations positives de puissance modérée sont retrouvées entre IL-6 et dépression, IL-6 et alcool, IL-1RA et cognition, IL-8 et dépression, IL-8 et alcool, sIL-2R et cannabis. Notre étude révèle que la réponse inflammatoire est activée chez les schizophrènes et toxicomanes. De plus, la toxicomanie semble jouer un rôle facilitant ou potentialisateur dans les augmentations des taux circulants d’IL-1RA. Les études en cours sur différentes populations de schizophrènes avec ou sans toxicomanie, et chez des toxicomanes non schizophrènes permettront de préciser le rôle des différentes drogues d’abus dans le syndrome inflammatoire chez les schizophrènes, ainsi que les implications de ce syndrome sur le plan clinique et thérapeutique. / Schizophrenia is a psychosis which presents a frequent comorbidity with substance use disorders (SUD) and with various immune alterations. Using meta-analysis, we have demonstrated previously establishment of an inflammatory syndrome in schizophrenia patients, illustrated by elevated circulating levels of IL-6 (a pro-inflammatory cytokine), sIL-2R (marker of immune activation) and IL-1RA (an anti-inflammatory cytokine). SUD is also associated with dysregulation of inflammatory cytokines, but the effects may depend on the type of substance of abuse. The goal of this project was: 1) To measure plasma concentrations of inflammatory cytokines in schizophrenia patients with comorbid SUD, before, during and after treatment with an atypical antipsychotic, quetiapine; and 2) To perform correlation studies between plasma concentrations of inflammatory cytokines and clinical symptoms, including positive and negative symptoms, cognition, depression and substance use. Relative to normal controls, patients with a dual diagnosis showed increased plasma concentrations of IL-6, IL-1RA, sIL-2R, and IL-8 at baseline, IL-1RA increases being the most important. Quetiapine treatment did not influence plasma cytokine concentrations, except sIL-2R which increased further. Moderate positive correlations were found between IL-6 and depression, IL-6 and alcohol, IL-1RA and cognition, IL-8 and depression, IL-8 and alcohol and between sIL-2R and cannabis. This study demonstrates that the immune and inflammatory response is activated in schizophrenia patients with comorbid SUD. Furthermore, SUD may play a facilitating or potentiating role in the increases in peripheral levels of IL-1RA. Ongoing studies in different patient populations with schizophrenia with or without SUD, and patients with SUD alone will help elucidate the role of different substances of abuse in the inflammatory syndrome in schizophrenia, as well as the clinical and therapeutic relevance of this syndrome.
|
209 |
Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice : Clinical and Experimental Studies with Special Emphasis on the Cellular Immune ResponseÖsterberg, Johanna January 2005 (has links)
<p>Patients with peritonitis or malignant obstructive jaundice (HPB<sup>+</sup>) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.</p><p>BT occurred infrequently in patients with acute peritonitis and in HPB<sup>+</sup> there was no evidence of BT. Peritonitis and HPB<sup>+ </sup>causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB<sup>+ </sup>a high rate of apoptosis in MLNs was observed. </p><p>An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB<sup>+</sup>.<sup> </sup>Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.</p>
|
210 |
Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice : Clinical and Experimental Studies with Special Emphasis on the Cellular Immune ResponseÖsterberg, Johanna January 2005 (has links)
Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs. BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed. An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.
|
Page generated in 0.0358 seconds