Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox

Journal of Inflammation

Research

Oliver R Oakley¹  Mohammad Bani-Ahmad¹  Mohammed S Inayat¹  Ismail S El-Amouri¹  Vincent S Gallicchio²  Howard L Elford³ 

[1] Department of Clinical Sciences, University of Kentucky, 40536, Lexington, KY, USA;Departments of Biological Sciences and Public Health Sciences, Clemson University, 29634, Clemson, SC, USA;Molecules for Health, Inc., 23219, Richmond, VA, USA;

关键词: Ribonucleotide Reductase;    Mixed Lymphocyte Reaction;    Post Stimulation;    Ribonucleotide Reductase Inhibitor;    Graft Versus Leukemia;   

DOI  :  10.1186/1476-9255-7-43

 received in 2010-04-05, accepted in 2010-08-18,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGraft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle.MethodsThe allogeneic mixed lymphocyte reaction (MLR) is a unique ex vivo method to study a drug's action on the initial events resulting in T-cell activation and proliferation, synonymous to the initial stages of tissue and organ destruction by T-cell responses in organ rejection and Graft-versus-host disease. Using this approach, we examined the effectiveness of two ribonucleotide reductase inhibitors (RRI), Didox and Trimidox, to inhibit T-cell activation and proliferation.ResultsThe compounds caused a marked reduction in the proliferative responses of T-cells, which is also accompanied by decreased secretion of cytokines IL-6, IFN-γ, TNF-α, IL-2, IL-13, IL-10 and IL-4.ConclusionsIn conclusion, these data provide critical information to justify further investigation into the potential use of these compounds post allogeneic bone marrow transplantation to alleviate graft-versus-host disease thereby achieving better outcomes.

【 授权许可】

Unknown   
© Inayat et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.