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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Main Authors: A. C. Knulst, G. J. M. Tibbe, C. Bril-Bazuin, E. G. Breedland, A. van Oudenaren, R. Benner, H. F. J. Savelkoul
Format: Article
Language:English
Published: Hindawi Limited 1994-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/S0962935194000062
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spelling 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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