Interleukin 7 worsens graft-versus-host disease

Manoj L. Sinha, Terry J. Fry, Daniel H. Fowler, Georgina Miller, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic bone marrow transplantation (BMT). The identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an 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 affected 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 BM transplant recipients, but not in animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host 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 use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on immune competence with the least toxicity.

Original languageEnglish (US)
Pages (from-to)2642-2649
Number of pages8
JournalBlood
Volume100
Issue number7
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Interleukin-7
Graft vs Host Disease
Grafts
T-cells
Bone Marrow Transplantation
T-Lymphocytes
Bone
Homologous Transplantation
Graft vs. host reactions
Toxicity
Tissue
Transplants
Mental Competency
Animals
Therapeutics
Cytokines
Inflammation

ASJC Scopus subject areas

  • Hematology

Cite this

Sinha, M. L., Fry, T. J., Fowler, D. H., Miller, G., & Mackall, C. L. (2002). Interleukin 7 worsens graft-versus-host disease. Blood, 100(7), 2642-2649. https://doi.org/10.1182/blood-2002-04-1082

Interleukin 7 worsens graft-versus-host disease. / Sinha, Manoj L.; Fry, Terry J.; Fowler, Daniel H.; Miller, Georgina; Mackall, Crystal L.

In: Blood, Vol. 100, No. 7, 01.10.2002, p. 2642-2649.

Research output: Contribution to journalArticle

Sinha, ML, Fry, TJ, Fowler, DH, Miller, G & Mackall, CL 2002, 'Interleukin 7 worsens graft-versus-host disease', Blood, vol. 100, no. 7, pp. 2642-2649. https://doi.org/10.1182/blood-2002-04-1082
Sinha ML, Fry TJ, Fowler DH, Miller G, Mackall CL. Interleukin 7 worsens graft-versus-host disease. Blood. 2002 Oct 1;100(7):2642-2649. https://doi.org/10.1182/blood-2002-04-1082
Sinha, Manoj L. ; Fry, Terry J. ; Fowler, Daniel H. ; Miller, Georgina ; Mackall, Crystal L. / Interleukin 7 worsens graft-versus-host disease. In: Blood. 2002 ; Vol. 100, No. 7. pp. 2642-2649.
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