Role of cytokines in resistance to African trypanosomes
The expression and role of cytokines in resistance to experimental <i>Trypanosoma congolense</i> infections in the highly susceptible BALB/c and relatively resistant C57BL/6 mice was studied. Higher levels of IL-4, IL-10 and IFN-ã were detected in the plasma of infected BALB/c than in C5...
Main Author: | |
---|---|
Other Authors: | |
Format: | Others |
Language: | en |
Published: |
University of Saskatchewan
1998
|
Online Access: | http://library.usask.ca/theses/available/etd-10212004-001451 |
id |
ndltd-USASK-oai-usask.ca-etd-10212004-001451 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-USASK-oai-usask.ca-etd-10212004-0014512013-01-08T16:31:51Z Role of cytokines in resistance to African trypanosomes Uzonna, Jude Ezeh The expression and role of cytokines in resistance to experimental <i>Trypanosoma congolense</i> infections in the highly susceptible BALB/c and relatively resistant C57BL/6 mice was studied. Higher levels of IL-4, IL-10 and IFN-ã were detected in the plasma of infected BALB/c than in C57BL/6 mice. In contrast, plasma levels of TNF-á were higher in C57BL/6 than in BALB/c mice. IL-10 and IFN-ã mRNA transcripts accumulated earlier and in higher concentrations in the spleens of susceptible than in resistant mice. TNF-á mRNA levels in the spleens were similar, but the hepatic TNF-á mRNA levels were higher in resistant than in susceptible mice on day 9. The kinetics of IL-4, IL-10 and IFN-ã spot-forming cells in the spleens were essentially similar but significantly higher numbers were detected in BALB/c than in C57BL/6 mice. Unstimulated and concanavalin A (Con A)-stimulated splenocytes from BALB/c mice secreted high amounts of IL-4, IL-10 and IFN-ã in cultures starting from day 4. Secretion of IL-4 by splenocytes from infected C57BL/6 mice was undetectable throughout the period tested. Secretion of IL-10 and IFN-ã became appreciable on day 6 but were down regulated by day 8. Treatment of infected BALB/c mice with Berenil resulted in cure and caused a dramatic decline in the secretion of IL-10 and IFN-ã by BALB/c splenocytes. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Anti-IL-10 or anti-IFN-ã antibodies effectively reversed this suppression. Whereas in vivo administrations of anti-IL-10 antibodies to BALB/c mice early during infection only moderately prolonged their survival period, anti-IFN-ã antibodies shifted the phenotype of susceptible BALB/c mice to a resistant-like phenotype. Most of the IL-4, IL-10 and IFN-ã found in the infected BALB/c mice were produced by adherent Thy1.2$\sp+$CD4$\sp-8\sp-$ splenocytes in synergy with adherent Thy1.2$\sp-$ cells. These adherent cells suppressed T and B cell responses. Infected BALB/c mice mounted an earlier IgM response to various antigens of T. congolense than did C57BL/6 mice. In contrast, C57BL/6 mice made a strong and sustained IgG2a and IgG3 response to these antigens. It is hypothesized that resistance to T. congolense infection in mice is mediated by a TH1 cell response. Tabel, Henry University of Saskatchewan 1998-01-01 text application/pdf http://library.usask.ca/theses/available/etd-10212004-001451 http://library.usask.ca/theses/available/etd-10212004-001451 en unrestricted I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
collection |
NDLTD |
language |
en |
format |
Others
|
sources |
NDLTD |
description |
The expression and role of cytokines in resistance to experimental <i>Trypanosoma congolense</i> infections in the highly susceptible BALB/c and relatively resistant C57BL/6 mice was studied. Higher levels of IL-4, IL-10 and IFN-ã were detected in the plasma of infected BALB/c than in C57BL/6 mice. In contrast, plasma levels of TNF-á were higher in C57BL/6 than in BALB/c mice. IL-10 and IFN-ã mRNA transcripts accumulated earlier and in higher concentrations in the spleens of susceptible than in resistant mice. TNF-á mRNA levels in the spleens were similar, but the hepatic TNF-á mRNA levels were higher in resistant than in susceptible mice on day 9. The kinetics of IL-4, IL-10 and IFN-ã spot-forming cells in the spleens were essentially similar but significantly higher numbers were detected in BALB/c than in C57BL/6 mice. Unstimulated and concanavalin A (Con A)-stimulated splenocytes from BALB/c mice secreted high amounts of IL-4, IL-10 and IFN-ã in cultures starting from day 4. Secretion of IL-4 by splenocytes from infected C57BL/6 mice was undetectable throughout the period tested. Secretion of IL-10 and IFN-ã became appreciable on day 6 but were down regulated by day 8. Treatment of infected BALB/c mice with Berenil resulted in cure and caused a dramatic decline in the secretion of IL-10 and IFN-ã by BALB/c splenocytes. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Anti-IL-10 or anti-IFN-ã antibodies effectively reversed this suppression. Whereas in vivo administrations of anti-IL-10 antibodies to BALB/c mice early during infection only moderately prolonged their survival period, anti-IFN-ã antibodies shifted the phenotype of susceptible BALB/c mice to a resistant-like phenotype. Most of the IL-4, IL-10 and IFN-ã found in the infected BALB/c mice were produced by adherent Thy1.2$\sp+$CD4$\sp-8\sp-$ splenocytes in synergy with adherent Thy1.2$\sp-$ cells. These adherent cells suppressed T and B cell responses. Infected BALB/c mice mounted an earlier IgM response to various antigens of T. congolense than did C57BL/6 mice. In contrast, C57BL/6 mice made a strong and sustained IgG2a and IgG3 response to these antigens. It is hypothesized that resistance to T. congolense infection in mice is mediated by a TH1 cell response. |
author2 |
Tabel, Henry |
author_facet |
Tabel, Henry Uzonna, Jude Ezeh |
author |
Uzonna, Jude Ezeh |
spellingShingle |
Uzonna, Jude Ezeh Role of cytokines in resistance to African trypanosomes |
author_sort |
Uzonna, Jude Ezeh |
title |
Role of cytokines in resistance to African trypanosomes |
title_short |
Role of cytokines in resistance to African trypanosomes |
title_full |
Role of cytokines in resistance to African trypanosomes |
title_fullStr |
Role of cytokines in resistance to African trypanosomes |
title_full_unstemmed |
Role of cytokines in resistance to African trypanosomes |
title_sort |
role of cytokines in resistance to african trypanosomes |
publisher |
University of Saskatchewan |
publishDate |
1998 |
url |
http://library.usask.ca/theses/available/etd-10212004-001451 |
work_keys_str_mv |
AT uzonnajudeezeh roleofcytokinesinresistancetoafricantrypanosomes |
_version_ |
1716531940934287360 |