The sigma ligand SR 31747 prevents the development of acute graft-versus-host disease in mice by blocking IFN-gamma and GM-CSF mRNA expression.
SR 31747 is a sigma ligand which prevents the development of acute graft-versus-host reaction (GvHR) in hybrid B6D2F1 mice injected with C57BL/6 parental spleen cells. In the present study, we showed that this drug dramatically impaired the GvHR-associated increase in the numbers of both B-lymphocytes and polymorphonuclear cells (PMNs) in the spleen. Because SR 31747 blocked the GvHR-induced expression of both interleukin-2 and transferrin receptors on T-lymphocytes, it is very likely that this molecule prevented the disease through an inhibition of T-lymphocyte activation. Cytokine messenger RNA analyses on spleen cells revealed that SR 31747 blocked IFN-gamma and GM-CSF but not IL-4 transcription. These effects, which are different from those observed with either cyclosporin-A or dexamethasone, strongly suggest that SR 31747 preferentially inhibits the Th1 lymphocyte subset.
Carayon
P
P
Immunology Department, Sanofi Recherche, Montpellier, France.
Bouaboula
M
M
Loubet
J F
JF
Bourrie
B
B
Petitpretre
G
G
Le Fur
G
G
Casellas
P
P
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D003510:Cyclohexanes / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000235:genetics; D007371:Interferon-gamma / Q000187:drug effects* / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects; D017480:Receptors, sigma / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*
D003510:Cyclohexanes; D016207:Cytokines; D012333:RNA, Messenger; D017480:Receptors, sigma; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C088447:SR 31747