Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.
Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.
Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Rainer
R
Noth
Robert
R
Häsler
Eckhard
E
Stüber
Mark
M
Ellrichmann
Heiner
H
Schäfer
Claudia
C
Geismann
Jochen
J
Hampe
Burkhard
B
Bewig
Thilo
T
Wedel
Martina
M
Böttner
Stefan
S
Schreiber
Philip
P
Rosenstiel
Alexander
A
Arlt
D000818:Animals; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005973:Glutamine / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D051379:Mice; D062793:Occludin / Q000096:biosynthesis; D010539:Permeability / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D062793:Occludin; C568986:Ocln protein, mouse; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine