DECREASED INTERLEUKIN-10 AND INCREASED INTERFERON-GAMMA PRODUCTION INPATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Ex vivo production of interleukin 10 (IL-10) and interferon-gamma (IFN -gamma) was investigated in patients with (n = 5) or without (n = 5) c hronic graft-versus-host disease (cGVHD) after allogeneic BMT, Patient s 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/10(6) MNC; 400 pg/10(6) MNC) was signif icantly reduced compared to patients without cGVHD (646-2662 pg/10(6) MNC; 1314 pg/10(6) MNC; P < 0.05) or healthy controls (679-6361 pg/10( 6) MNC; 3054 pg/10(6) MNC, P < 0.01), In vitro inhibition of IL-10 by an anti-IL-10 monoclonal antibody enhanced the release of IFN-gamma by anti-CD3-stimulated MNCs from 354 +/- 34 pg/10(6) MNCs to 899 +/- 61 pg/10(6) MNCs. Thus, low IL-10 production may cause high IFN-gamma rel ease, In anti-CD3-activated MNCs obtained from patients with cGVHD IFN -gamma production was significantly increased (324-3331 pg/10(6) MNC; 1849 pg/10(6) C) compared to healthy donors (127-900 pg/10(6) MNC; 305 pg/10(6) MNC P < 0.01), In addition, median IFN-gamma release by anti -CD3-activated MNCs obtained from patients without cGVHD (464 pg/10(6) MNC) was about five-fold lower than in patients with cGVHD, In contra st to cytokine production, the differential leukocyte count (percentag es of monocytes, T cells and CD4/CD8 ratio) was essentially the same b oth in patients with or without cGVHD, Thus, a different activation of Th-l and Th-2 cells by anti-CD3 may be responsible for the deviant cy tokine productions in patients with cGVHD, In conclusion, we observed significantly decreased IL-10 production in patients with cGVHD and an increased median IFN-gamma secretion, which may contribute to the alt ered cytokine production after allogeneic BMT leading to cGVHD. Thus, supplementing IL-10 may become a new strategy for preventing cGVHD.