Decreased interleukin 10 and increased interferon-gamma production in patients 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) 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/10(6) MNC; 400 pg/10(6) MNC) was significantly 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 release. 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) MNC) 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 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 patinets with cGVHD and an increased median IFN-gamma 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.
Körholz
D
D
Department of Pediatric Hematology and Oncology, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
Kunst
D
D
Hempel
L
L
Söhngen
D
D
Heyll
A
A
Bönig
H
H
Göbel
U
U
Zintl
F
F
Burdach
S
S
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
D016753:Interleukin-10; D007371:Interferon-gamma