PMID- 21108989
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20131121
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 39
IP  - 2
DP  - 2011 Feb
TI  - Steroid treatment alters adhesion molecule and chemokine expression in
      experimental acute graft-vs.-host disease of the intestinal tract.
PG  - 238-249.e1
LID - 10.1016/j.exphem.2010.11.006 [doi]
AB  - OBJECTIVE: Acute graft-vs.-host disease (aGVHD) is a major complication after
      allogeneic bone marrow transplantation (allo-BMT) that is characterized by high
      morbidity and mortality. Systemic treatment with steroids has been the mainstay
      of first-line therapy of aGVHD, although controlled experimental data in this
      context are limited. MATERIALS AND METHODS: Using a haploidentical murine BMT
      model, steroid effects on hepatic and intestinal inflammation during aGVHD have
      been investigated. Lethally irradiated B6D2F1 mice received bone marrow cells and
      splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors.
      RESULTS: Intraperitoneal administration of prednisolone (2 mg/kg body weight
      every day) early after onset of GVHD from day +10 until day +42 resulted in
      reduced clinical GVHD severity and improved survival of allogeneic recipients.
      Although the liver was barely affected by prednisolone treatment, aGVHD-related
      histopathologic injury of the gastrointestinal tract was strongly reduced in
      association with diminished expression of interferon-gamma, tumor necrosis
      factor, CXCL 9-11, CCL2-3, mucosal addressin cell adhesion molecule-1, and
      intercellular adhesion molecule-1. Prednisolone-induced reduction of adhesion
      molecule expression in the gut manifested earlier than seen for cytokines or
      chemokines. Interestingly, when starting steroid treatment on day +28, the course
      of GVHD was unchanged and no major differences in cyto- or chemokine expression
      in gastrointestinal tract or liver on day +42 were seen. CONCLUSIONS: When
      started early after GVHD onset, prednisolone-related beneficial effects can
      affect aGVHD target organs differently, involving divergent regulation of
      inflammation and leukocyte migration. Specifically, a change in adhesion
      properties between leukocytes and endothelial cells in the gastrointestinal tract
      may be one of the initial steps in a cascade of steroid-related aGVHD-attenuating
      events.
CI  - Copyright (c) 2011 ISEH - Society for Hematology and Stem Cells. Published by
      Elsevier Inc. All rights reserved.
FAU - Bouazzaoui, Abdellatif
AU  - Bouazzaoui A
AD  - Department of Hematology and Oncology, University of Regensburg Medical School,
      Regensburg, Germany.
FAU - Spacenko, Elena
AU  - Spacenko E
FAU - Mueller, Gunnar
AU  - Mueller G
FAU - Huber, Elisabeth
AU  - Huber E
FAU - Schubert, Thomas
AU  - Schubert T
FAU - Holler, Ernst
AU  - Holler E
FAU - Andreesen, Reinhard
AU  - Andreesen R
FAU - Hildebrandt, Gerhard C
AU  - Hildebrandt GC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101122
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation
MH  - Cell Adhesion Molecules/*metabolism
MH  - Chemokines/*metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Gastrointestinal Tract/*drug effects/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Graft vs Host Disease/*drug therapy
MH  - *Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Intestinal Diseases/drug therapy
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Prednisone/pharmacology/therapeutic use
MH  - Survival Analysis
MH  - T-Lymphocytes/cytology/immunology
EDAT- 2010/11/27 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/11/27 06:00
PHST- 2010/04/28 00:00 [received]
PHST- 2010/11/10 00:00 [revised]
PHST- 2010/11/11 00:00 [accepted]
PHST- 2010/11/27 06:00 [entrez]
PHST- 2010/11/27 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - S0301-472X(10)00553-9 [pii]
AID - 10.1016/j.exphem.2010.11.006 [doi]
PST - ppublish
SO  - Exp Hematol. 2011 Feb;39(2):238-249.e1. doi: 10.1016/j.exphem.2010.11.006. Epub
      2010 Nov 22.