Email updates

Keep up to date with the latest news and content from Journal of Inflammation and BioMed Central.

Open Access Open Badges Research

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

Mohammed S Inayat1, Ismail S El-Amouri1, Mohammad Bani-Ahmad1, Howard L Elford2, Vincent S Gallicchio3 and Oliver R Oakley1*

Author Affiliations

1 Department of Clinical Sciences, University of Kentucky, Lexington, KY 40536, USA

2 Molecules for Health, Inc., Richmond, VA 23219, USA

3 Departments of Biological Sciences and Public Health Sciences, Clemson University, Clemson, SC 29634, USA

For all author emails, please log on.

Journal of Inflammation 2010, 7:43  doi:10.1186/1476-9255-7-43

Published: 18 August 2010



Graft-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.


The 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.


The 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.


In 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.