Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice
A murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-γ and TNF-α. Lethally irradiated (C57BL × CBA)F1 mice were reconstituted eit...
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1994-01-01
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Online Access: | http://dx.doi.org/10.1155/S0962935194000062 |
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doaj-d38c39f78ef54b509299f730e6aee1ef2020-11-24T21:17:03ZengHindawi LimitedMediators of Inflammation0962-93511466-18611994-01-0131334010.1155/S0962935194000062Cytokine Detection and Modulation in Acute Graft vs. Host Disease in MiceA. C. Knulst0G. J. M. Tibbe1C. Bril-Bazuin2E. G. Breedland3A. van Oudenaren4R. Benner5H. F. J. Savelkoul6Department of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University, Rotterdam, The NetherlandsA murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-γ and TNF-α. Lethally irradiated (C57BL × CBA)F1 mice were reconstituted either with 107 allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-α and IFN-γ levels was found in allogeneically reconstituted mice. This is in contrast to the syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice IL-6, IFN-γ and TNF-α concentrations were increased. The expression of mRNA for cytokines as detected by reverse transcription PCR was studied in spleen cells. In the allogeneic reconstituted mice the mRNA expression of IL-1α, IL-2, IL-6, IFN-γ and TNF-α displayed faster kinetics compared with that in syngeneic reconstituted mice. The effect of treatment with recombinant cytokines, antibodies to cytokines and to cytokine receptors on the development of GVHD was investigated. Administration of recombinant IL-2 to allogeneically reconstituted mice strongly increased the morbidity and mortality whereas injection of IL-1α and TNF-α did not influence survival. Administration of antibodies against IL-2 or the IL-2 receptor decreased the morbidity and mortality. Anti-IL-6, anti-IFN-γ, and anti-TNF-α mAB, on the other hand, did not affect the morbidity and mortality of GVHD. The results of this study suggest successive waves of cytokine-secreting cell populations consistent with the induction of an inflammatory response in the development of acute GVH disease.http://dx.doi.org/10.1155/S0962935194000062 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
A. C. Knulst G. J. M. Tibbe C. Bril-Bazuin E. G. Breedland A. van Oudenaren R. Benner H. F. J. Savelkoul |
spellingShingle |
A. C. Knulst G. J. M. Tibbe C. Bril-Bazuin E. G. Breedland A. van Oudenaren R. Benner H. F. J. Savelkoul Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice Mediators of Inflammation |
author_facet |
A. C. Knulst G. J. M. Tibbe C. Bril-Bazuin E. G. Breedland A. van Oudenaren R. Benner H. F. J. Savelkoul |
author_sort |
A. C. Knulst |
title |
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice |
title_short |
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice |
title_full |
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice |
title_fullStr |
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice |
title_full_unstemmed |
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice |
title_sort |
cytokine detection and modulation in acute graft vs. host disease in mice |
publisher |
Hindawi Limited |
series |
Mediators of Inflammation |
issn |
0962-9351 1466-1861 |
publishDate |
1994-01-01 |
description |
A murine model for acute lethal graft vs. host disease (GVHD) was
used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-γ and TNF-α. Lethally irradiated (C57BL × CBA)F1 mice were reconstituted either with 107 allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-α and IFN-γ levels was found in allogeneically reconstituted mice. This is in contrast to the
syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice
IL-6, IFN-γ and TNF-α concentrations were increased. The
expression of mRNA for cytokines as detected by reverse
transcription PCR was studied in spleen cells. In the allogeneic
reconstituted mice the mRNA expression of IL-1α, IL-2, IL-6,
IFN-γ and TNF-α displayed faster kinetics compared with
that in syngeneic reconstituted mice. The effect of treatment with
recombinant cytokines, antibodies to cytokines and to cytokine
receptors on the development of GVHD was investigated.
Administration of recombinant IL-2 to allogeneically reconstituted
mice strongly increased the morbidity and mortality whereas
injection of IL-1α and TNF-α did not influence survival.
Administration of antibodies against IL-2 or the IL-2 receptor
decreased the morbidity and mortality. Anti-IL-6, anti-IFN-γ,
and anti-TNF-α mAB, on the other hand, did not affect the
morbidity and mortality of GVHD. The results of this study suggest
successive waves of cytokine-secreting cell populations consistent
with the induction of an inflammatory response in the development of
acute GVH disease. |
url |
http://dx.doi.org/10.1155/S0962935194000062 |
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