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Graft-Versus-Host Disease

Decreased interleukin 10 and increased interferon-γ production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation

Abstract

Ex vivo production of interleukin 10 (IL-10) and interferon-γ (IFN-γ) was investigated in patients with (n = 5) or without (n = 5) chronic graft-versus-host disease (cGVHD) after allogeneic BMT. Patients were matched for time after transplantation and type of transplant. Anti-CD3-induced IL-10 production in MNCs isolated from patients with cGVHD (range/median: 26–650 pg/106 MNC; 400 pg/106 MNC) was significantly reduced compared to patients without cGVHD (646–2662 pg/106 MNC; 1314 pg/106 MNC; P < 0.05) or healthy controls (679–6361 pg/106 MNC; 3054 pg/106 MNC, P < 0.01). In vitro inhibition of IL-10 by an anti-IL-10 monoclonal antibody enhanced the release of IFN-γ by anti-CD3-stimulated MNCs from 354 ± 34 pg/106 MNCs to 899 ± 61 pg/106 MNCs. Thus, low IL-10 production may cause high IFN- γ release. In anti-CD3-activated MNCs obtained from patients with cGVHD IFN- γ production was significantly increased (324–3331 pg/106 MNC; 1849 pg/106 MNC) compared to healthy donors (127–900 pg/106 MNC; 305 pg/106 MNC P < 0.01). in addition, median ifn-γ release by anti-CD3-activated MNCs obtained from patients without cGVHD (464 pg/106 MNC) was about five-fold lower than in patients with cGVHD. In contrast to cytokine production, the differential leukocyte count (percentages of monocytes, T cells and CD4/CD8 ratio) was essentially the same both in patients with or without cGVHD. Thus, a different activation of Th-1 and Th-2 cells by anti-CD3 may be responsible for the deviant cytokine productions in patients with cGVHD. In conclusion, we observed significantly decreased IL-10 production in patients with cGVHD and an increased median IFN-γ secretion, which may contribute to the altered cytokine production after allogeneic BMT leading to cGVHD. Thus, supplementing IL-10 may become a new strategy for preventing cGVHD.

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Körholz, D., Kunst, D., Hempel, L. et al. Decreased interleukin 10 and increased interferon-γ production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation. Bone Marrow Transplant 19, 691–695 (1997). https://doi.org/10.1038/sj.bmt.1700718

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  • DOI: https://doi.org/10.1038/sj.bmt.1700718

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