No Cover Image

E-Thesis 153 views 646 downloads

Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells. / Michael Pynn

Swansea University Author: Michael Pynn

Abstract

Introduction: Obesity and asthma are associated but the mechanism is poorly understood. Enhanced systemic inflammation may underlie the obesity-asthma paradigm. Although there is good mechanistic data that obesity augments the immune response as well as promoting immune dysregulation by reducing reg...

Full description

Published: 2014
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42704
Tags: Add Tag
No Tags, Be the first to tag this record!
first_indexed 2018-08-02T18:55:20Z
last_indexed 2019-10-21T16:48:18Z
id cronfa42704
recordtype RisThesis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2018-08-29T15:09:55.4479861</datestamp><bib-version>v2</bib-version><id>42704</id><entry>2018-08-02</entry><title>Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.</title><swanseaauthors><author><sid>1ad559980330c0d8190cb83e704a8e57</sid><ORCID>NULL</ORCID><firstname>Michael</firstname><surname>Pynn</surname><name>Michael Pynn</name><active>true</active><ethesisStudent>true</ethesisStudent></author></swanseaauthors><date>2018-08-02</date><abstract>Introduction: Obesity and asthma are associated but the mechanism is poorly understood. Enhanced systemic inflammation may underlie the obesity-asthma paradigm. Although there is good mechanistic data that obesity augments the immune response as well as promoting immune dysregulation by reducing regulatory T cell numbers, there is little work relating this to obesity and asthma. Methods: A case-control study examined 6 groups of pre-menopausal women (n=84); non-obese, f overweight and obese individuals with and without asthma. Measures of adiposity and lung function I were taken and peripheral blood collected during the first 7 days of the menstrual cycle. Innate immune parameters measured included: full blood count and differential; chemiluminescence recorded whole blood reactive oxygen species; neutrophil related cytokines; neutrophil and i monocyte activation markers by flow cytometry, and LPS induced whole blood cytokine responses. Insulin resistance, adipokine levels and free fatty acid levels were recorded. Dendritic cell and lymphocyte subtypes including FoxP33+ regulatory T cells (Tregs) were quantified by flow cytometry I and PHA-induced cytokine responses measured in whole blood. Results: Obesity and asthma appeared to have synergistic effects with regards to circulating I neutrophil count, plasma IL-6 and leptin with obese asthmatics having the highest levels. Reactive I oxygen species production followed a similar trend. Increasing BMI within asthmatics was associated f with a reduction in eosinophils and myeloid dendritic cells, and increased PHA-induced IFNy. Obesity I across the entire study group was associated with increased neutrophil counts and neutrophil P related cytokines, reduced FoxPS3+Tregs and increased PHA-induced IL-17 response. Conclusions: Systemic changes in immunity occur in obesity and asthma; some of these are additive. Within asthmatics, obesity is associated with responses suggesting T helper 1 (Th1) rather than Th2 bias. Obesity-associated systemic changes in immunity might encourage a loss of immune tolerance. These findings suggest that obesity might mediate its effects in asthma through systemic inflammatory mechanisms.</abstract><type>E-Thesis</type><journal/><journalNumber></journalNumber><paginationStart/><paginationEnd/><publisher/><placeOfPublication/><isbnPrint/><issnPrint/><issnElectronic/><keywords>Medicine.;Immunology.</keywords><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2014</publishedYear><publishedDate>2014-12-31</publishedDate><doi/><url/><notes/><college>COLLEGE NANME</college><department>Swansea University Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><apcterm/><lastEdited>2018-08-29T15:09:55.4479861</lastEdited><Created>2018-08-02T16:24:30.1802054</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Michael</firstname><surname>Pynn</surname><orcid>NULL</orcid><order>1</order></author></authors><documents><document><filename>0042704-02082018162515.pdf</filename><originalFilename>10807473.pdf</originalFilename><uploaded>2018-08-02T16:25:15.4070000</uploaded><type>Output</type><contentLength>20313728</contentLength><contentType>application/pdf</contentType><version>E-Thesis</version><cronfaStatus>true</cronfaStatus><embargoDate>2018-08-02T16:25:15.4070000</embargoDate><copyrightCorrect>false</copyrightCorrect></document></documents><OutputDurs/></rfc1807>
spelling 2018-08-29T15:09:55.4479861 v2 42704 2018-08-02 Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells. 1ad559980330c0d8190cb83e704a8e57 NULL Michael Pynn Michael Pynn true true 2018-08-02 Introduction: Obesity and asthma are associated but the mechanism is poorly understood. Enhanced systemic inflammation may underlie the obesity-asthma paradigm. Although there is good mechanistic data that obesity augments the immune response as well as promoting immune dysregulation by reducing regulatory T cell numbers, there is little work relating this to obesity and asthma. Methods: A case-control study examined 6 groups of pre-menopausal women (n=84); non-obese, f overweight and obese individuals with and without asthma. Measures of adiposity and lung function I were taken and peripheral blood collected during the first 7 days of the menstrual cycle. Innate immune parameters measured included: full blood count and differential; chemiluminescence recorded whole blood reactive oxygen species; neutrophil related cytokines; neutrophil and i monocyte activation markers by flow cytometry, and LPS induced whole blood cytokine responses. Insulin resistance, adipokine levels and free fatty acid levels were recorded. Dendritic cell and lymphocyte subtypes including FoxP33+ regulatory T cells (Tregs) were quantified by flow cytometry I and PHA-induced cytokine responses measured in whole blood. Results: Obesity and asthma appeared to have synergistic effects with regards to circulating I neutrophil count, plasma IL-6 and leptin with obese asthmatics having the highest levels. Reactive I oxygen species production followed a similar trend. Increasing BMI within asthmatics was associated f with a reduction in eosinophils and myeloid dendritic cells, and increased PHA-induced IFNy. Obesity I across the entire study group was associated with increased neutrophil counts and neutrophil P related cytokines, reduced FoxPS3+Tregs and increased PHA-induced IL-17 response. Conclusions: Systemic changes in immunity occur in obesity and asthma; some of these are additive. Within asthmatics, obesity is associated with responses suggesting T helper 1 (Th1) rather than Th2 bias. Obesity-associated systemic changes in immunity might encourage a loss of immune tolerance. These findings suggest that obesity might mediate its effects in asthma through systemic inflammatory mechanisms. E-Thesis Medicine.;Immunology. 31 12 2014 2014-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T15:09:55.4479861 2018-08-02T16:24:30.1802054 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Michael Pynn NULL 1 0042704-02082018162515.pdf 10807473.pdf 2018-08-02T16:25:15.4070000 Output 20313728 application/pdf E-Thesis true 2018-08-02T16:25:15.4070000 false
title Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
spellingShingle Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
Michael Pynn
title_short Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
title_full Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
title_fullStr Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
title_full_unstemmed Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
title_sort Obesity and asthma: The role of innate immunity, adipokines and regulatory T cells.
author_id_str_mv 1ad559980330c0d8190cb83e704a8e57
author_id_fullname_str_mv 1ad559980330c0d8190cb83e704a8e57_***_Michael Pynn
author Michael Pynn
author2 Michael Pynn
format E-Thesis
publishDate 2014
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Introduction: Obesity and asthma are associated but the mechanism is poorly understood. Enhanced systemic inflammation may underlie the obesity-asthma paradigm. Although there is good mechanistic data that obesity augments the immune response as well as promoting immune dysregulation by reducing regulatory T cell numbers, there is little work relating this to obesity and asthma. Methods: A case-control study examined 6 groups of pre-menopausal women (n=84); non-obese, f overweight and obese individuals with and without asthma. Measures of adiposity and lung function I were taken and peripheral blood collected during the first 7 days of the menstrual cycle. Innate immune parameters measured included: full blood count and differential; chemiluminescence recorded whole blood reactive oxygen species; neutrophil related cytokines; neutrophil and i monocyte activation markers by flow cytometry, and LPS induced whole blood cytokine responses. Insulin resistance, adipokine levels and free fatty acid levels were recorded. Dendritic cell and lymphocyte subtypes including FoxP33+ regulatory T cells (Tregs) were quantified by flow cytometry I and PHA-induced cytokine responses measured in whole blood. Results: Obesity and asthma appeared to have synergistic effects with regards to circulating I neutrophil count, plasma IL-6 and leptin with obese asthmatics having the highest levels. Reactive I oxygen species production followed a similar trend. Increasing BMI within asthmatics was associated f with a reduction in eosinophils and myeloid dendritic cells, and increased PHA-induced IFNy. Obesity I across the entire study group was associated with increased neutrophil counts and neutrophil P related cytokines, reduced FoxPS3+Tregs and increased PHA-induced IL-17 response. Conclusions: Systemic changes in immunity occur in obesity and asthma; some of these are additive. Within asthmatics, obesity is associated with responses suggesting T helper 1 (Th1) rather than Th2 bias. Obesity-associated systemic changes in immunity might encourage a loss of immune tolerance. These findings suggest that obesity might mediate its effects in asthma through systemic inflammatory mechanisms.
published_date 2014-12-31T03:53:29Z
_version_ 1763752657058529280
score 11.012678

Similar Items