Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects.
Blood
; 138(24): 2583-2588, 2021 12 16.
Article
en En
| MEDLINE
| ID: mdl-34424962
ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Hematopoyéticas
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Receptores de Interleucina-6
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Inhibidores del Factor de Necrosis Tumoral
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Enfermedad Injerto contra Huésped
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Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Blood
Año:
2021
Tipo del documento:
Article