A clinical phase I/II study of recombinant human interleukin-1 receptor in glucocorticoid-resistant graft-versus-host disease
| Autor: | Loretta A. Williams, Claudio Anasetti, Cindy Ippoliti, Josephine Yen, Consuelo Blosch, Philip L. Mccarthy, Margaret Harris-Bacile, Richard E. Champlin, Donna Przepiorka, Joseph W. Fay, Cindy Jacobs |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_treatment Drug Resistance Graft vs Host Disease Interleukin-1 receptor Proinflammatory cytokine Pathogenesis immune system diseases medicine Humans Glucocorticoids Bone Marrow Transplantation Transplantation Chemotherapy business.industry Interleukin Receptors Interleukin-1 Middle Aged medicine.disease Recombinant Proteins surgical procedures operative Graft-versus-host disease medicine.anatomical_structure Solubility Immunology Female Bone marrow business Glucocorticoid medicine.drug |
| Zdroj: | Transplantation. 62(5) |
| ISSN: | 0041-1337 |
| Popis: | Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation. GVHD is accompanied by the release of inflammatory cytokines, including interleukin (IL)-1, and previous work has demonstrated that IL-1 participates in the pathogenesis of GVHD. The recombinant human IL-1 receptor (rhuIL-1R) is the soluble form of the type I IL-1 receptor that can bind to IL-1 and prevent cellular activation. We report a phase I/II trial utilizing the rhuIL-1R in the treatment of allogeneic bone narrow transplant patients not improving with glucocorticoid therapy. RhuIL-R was given at four dose levels for 21 days to 14 patients with progressive or persistent acute GVHD. The study drug had no clinical or persistent hematopoiesis and the treatment was tolerated by patients without toxicity at all dose levels. Eight of 14 patients (57%) had an improvement of GVHD after rhuIL-1R therapy. Improvement in GVHD was noted at each dose level, although a dose-response effect for rhuIL-1R treatment was not observed. This work supports the concept that IL-1 plays a role in the inflammation associated with acute GVHD. A controlled study of the rhuIL-1R for treatment of prophylaxis of GVHD is warranted. |
| Databáze: | OpenAIRE |
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