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.

Abstract

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.

• Authors: P Carayon, M Bouaboula, J F Loubet, B Bourrie, G Petitpretre, G Le Fur, P Casellas
• Journal: International journal of immunopharmacology (Int J Immunopharmacol) Vol. 17 Issue 9 Pg. 753-61 (Sep 1995) ISSN: 0192-0561 [Print] England
• PMID: 8582787 (Publication Type: Journal Article)

Chemical References

• Cyclohexanes
• Cytokines
• RNA, Messenger
• Receptors, sigma
• Interferon-gamma
• Granulocyte-Macrophage Colony-Stimulating Factor
• SR 31747

Topics

• Acute Disease
• Animals
• Base Sequence
• Cyclohexanes (pharmacology)
• Cytokines (drug effects)
• Female
• Graft vs Host Disease (pathology, prevention & control)
• Granulocyte-Macrophage Colony-Stimulating Factor (drug effects, genetics)
• Interferon-gamma (drug effects, genetics)
• Leukocytes (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Molecular Sequence Data
• Polymerase Chain Reaction
• RNA, Messenger (drug effects)
• Receptors, sigma (metabolism)
• Spleen (cytology, drug effects)