TY - JOUR
T1 - Decreased interleukin 10 and increased interferon-γ production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation
AU - Körholz, D.
AU - Kunst, D.
AU - Hempel, L.
AU - Söhngen, D.
AU - Heyll, A.
AU - Bönig, H.
AU - Göbel, U.
AU - Zintl, F.
AU - Burdach, S.
N1 - Funding Information:
This study was supported by DFG grants Ko 971/3–2, He 2202/2– 2 and the DFG Sonderforschungsbereich 503.
PY - 1997/4/1
Y1 - 1997/4/1
N2 - 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.
AB - 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.
KW - Bone marrow transplantation
KW - Graft-versus-host disease
KW - Interferon-γ
KW - Interleukin 10
UR - http://www.scopus.com/inward/record.url?scp=1842405343&partnerID=8YFLogxK
U2 - 10.1038/sj.bmt.1700718
DO - 10.1038/sj.bmt.1700718
M3 - Article
C2 - 9156246
AN - SCOPUS:1842405343
SN - 0268-3369
VL - 19
SP - 691
EP - 695
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 7
ER -