Interleukin-1 or tumor necrosis factor-alpha antagonists do not inhibit graft-versus-host disease induced across the major histocompatibility barrier in mice.
We show that while interleukin-1 and tumor necrosis factor-alpha antagonists are partially able to inhibit graft-versus-host disease (GVHD) when bone marrow (BM) transplantation is performed in irradiated recipients of minor antigen-disparate donor BM, these same antagonists do not inhibit GVHD when donor BM is fully MHC disparate. This failure in MHC-disparate recipients occurs despite the presence of interleukin-1 and tumor necrosis factor-alpha mRNA in tissues of GVHD mice measured by in situ hybridization and despite escalation of antagonist dosages far beyond those used in previous reports. These findings indicate that a relationship may exist between cytokines that amplify GVHD and target antigens that elicit GVHD. Moreover, when GVHD inhibition was observed in the minor model, it was transient, which suggests that it may be important to target more than one cytokine to effectively inhibit GVHD. These findings suggest that caution is in order in clinical GVHD studies based entirely on anti-proinflammatory cytokine treatment.
Department of Therapeutic Radiology, University of Minnesota Hospital and Clinics, Minneapolis 55455, USA.
D A
DA
Vallera
P A
PA
Taylor
J L
JL
Vannice
A
A
Panoskaltsis-Mortari
B R
BR
Blazar
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D006648:Histocompatibility; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha