期刊
BLOOD
卷 114, 期 4, 页码 891-900出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-01-197178
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资金
- NHLBI NIH HHS [HL 081650, HL 064603, R01 HL064603, R01 HL081650] Funding Source: Medline
- NIAID NIH HHS [AI 078713, R01 AI078713, R56 AI078713] Funding Source: Medline
- NIDDK NIH HHS [R01 DK083358] Funding Source: Medline
Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation and is characterized by the overproduction of proinflammatory cytokines. In this study, we have identified interleukin-6 (IL-6) as a critical inflammatory cytokine that alters the balance between the effector and regulatory arms of the immune system and drives a proinflammatory phenotype that is a defining characteristic of GVHD. Our results demonstrate that inhibition of the IL-6 signaling pathway by way of antibody-mediated blockade of the IL-6 receptor (IL-6R) markedly reduces pathologic damage attributable to GVHD. This is accompanied by a significant increase in the absolute number of regulatory T cells (Tregs) that is due to augmentation of thymic-dependent and thymic-independent Treg production. Correspondingly, there is a significant reduction in the number of T helper 1 and T helper 17 cells in GVHD target organs, demonstrating that blockade of IL-6 signaling decreases the ratio of proinflammatory T cells to Tregs. These studies demonstrate that antibody blockade of the IL-6R serves to recalibrate the effector and regulatory arms of the immune system and represents a novel, potentially clinically translatable, strategy for the attenuation of GVHD. (Blood. 2009; 114: 891-900)
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