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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-04-1082. This Article Full Text (PDF) All Versions of this Article: 2002-04-1082v1 100/7/2642    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sinha, M. L Articles by Mackall, C. L Search for Related Content PubMed PubMed Citation Articles by Sinha, M. L Articles by Mackall, C. L Social Bookmarking                   What's this? Submitted April 10, 2002 Accepted May 16, 2002 Interleukin-7 worsens graft-vs-host disease Manoj L Sinha, Terry J Fry, Daniel H Fowler, Georgina Miller, and Crystal L Mackall* Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Veterinary Resources Program, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: cm35c{at}nih.gov. Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic BMT. The identification of therapies which can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. IL-7 is the most potent thymopoietic cytokine identified thus far. In order to study the effects of IL-7 on immune reconstitution and GVHD following allogeneic BMT, we administered rhIL-7 in a murine parent into F1 model. Results showed that rhIL-7 therapy lowered the "threshold" T cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 increased the degree of inflammation and tissue damage observed at all T cell doses studied, but did not change the pattern of organs effected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis in the setting of allogeneic T cell depleted (TCD) and T cell replete BMT. We observed that rhIL-7 therapy enhanced thymic function in TCD allogeneic BMT recipients, but not in animals which received even modest doses of T cells presumably due to thymic toxicity of the GVH reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use in the setting of allogeneic BMT. These results suggest that IL-7's use should be limited to the setting of TCD BMT in order to obtain the greatest benefit on immune competence with the least toxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Sutherland, L. Spyroglou, J. L. Muirhead, T. S. Heng, A. Prieto-Hinojosa, H. M. Prince, A. P. Chidgey, A. P. Schwarer, and R. L. Boyd Enhanced Immune System Regeneration in Humans Following Allogeneic or Autologous Hemopoietic Stem Cell Transplantation by Temporary Sex Steroid Blockade Clin. Cancer Res., February 15, 2008; 14(4): 1138 - 1149. [Abstract] [Full Text] [PDF] P. Reddy IL-7: griffinesque role in GVHD Blood, October 15, 2007; 110(8): 2788 - 2788. [Full Text] [PDF] B. Chung, E. P. Dudl, D. Min, L. Barsky, N. Smiley, and K. I. 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