TY - JOUR
T1 - Elevated inflammatory cytokine levels in bone marrow graft rejection
AU - Nagler, Arnon
AU - Or, R.
AU - Nisman, B.
AU - Kalickman, I.
AU - Slavin, S.
AU - Barak, V.
PY - 1995/11/15
Y1 - 1995/11/15
N2 - Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR). Seven of the patients underwent BMT from siblings (6 matched and 1 mismatched), 4 patients received bone marrow from other family members (3 mismatched and 1 matched), and 1 patient underwent HLA-matched unrelated BMT. Nine of 12 had a sex-mismatched BMT and 5/12 had an ABO-mismatched BMT. Nine of 12 underwent T cell-depleted (Campath anti-CDw52 moAb) BMT. Rejection was defined as marrow hypoplasia with a peripheral white blood cell count <0.5x 109/L 21 days after BMT, in coi\junction with the absence of donor cells by polymerase chain reaction analysis using a sex-mis-matched probe and/or a tumor-specific probe (BCR/ ABL). Twenty-five patients who underwent uneventful BMT with no GR served as controls. The levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) were evaluated by a high sensitive RIA or an enzyme immunoassay. The levels of TNF and IL-6 were found to be higher in 10/12 and 7/7 evaluated GR patients, respectively, as compared with controls (P<0.05). The level of IL-1 was high only in 2/12 patients. TNF elevation occurred in all patients immediately after GR. TNF and IL-6 levels were significantly higher for patients with early rejection (<35 days after BMT) as compared with patients with late rejection (>35 days after BMT) (P<0.049 and P<0.006, respectively). Eight patients engrafted after the second transplant (2 only transient). All 6 patients with stable engraftment are alive (4 with basic disease), while the 4 patients who did not engraft and the 2 patients with only transient engraftment died. In the 6 patients with no engraftment or only transient engraftment, the elevated TNF levels remained high; in the 6 patients who had stable engraftment after retransplant, TNF levels, but not IL-6 levels, decreased. In conclusion, a majority of the patients with GR displayed high levels of inflammatory cytokines (TNF and IL-6). Dysregulation of inflammatory cytokines may be involved in the pathogenesis of GR.
AB - Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR). Seven of the patients underwent BMT from siblings (6 matched and 1 mismatched), 4 patients received bone marrow from other family members (3 mismatched and 1 matched), and 1 patient underwent HLA-matched unrelated BMT. Nine of 12 had a sex-mismatched BMT and 5/12 had an ABO-mismatched BMT. Nine of 12 underwent T cell-depleted (Campath anti-CDw52 moAb) BMT. Rejection was defined as marrow hypoplasia with a peripheral white blood cell count <0.5x 109/L 21 days after BMT, in coi\junction with the absence of donor cells by polymerase chain reaction analysis using a sex-mis-matched probe and/or a tumor-specific probe (BCR/ ABL). Twenty-five patients who underwent uneventful BMT with no GR served as controls. The levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) were evaluated by a high sensitive RIA or an enzyme immunoassay. The levels of TNF and IL-6 were found to be higher in 10/12 and 7/7 evaluated GR patients, respectively, as compared with controls (P<0.05). The level of IL-1 was high only in 2/12 patients. TNF elevation occurred in all patients immediately after GR. TNF and IL-6 levels were significantly higher for patients with early rejection (<35 days after BMT) as compared with patients with late rejection (>35 days after BMT) (P<0.049 and P<0.006, respectively). Eight patients engrafted after the second transplant (2 only transient). All 6 patients with stable engraftment are alive (4 with basic disease), while the 4 patients who did not engraft and the 2 patients with only transient engraftment died. In the 6 patients with no engraftment or only transient engraftment, the elevated TNF levels remained high; in the 6 patients who had stable engraftment after retransplant, TNF levels, but not IL-6 levels, decreased. In conclusion, a majority of the patients with GR displayed high levels of inflammatory cytokines (TNF and IL-6). Dysregulation of inflammatory cytokines may be involved in the pathogenesis of GR.
UR - http://www.scopus.com/inward/record.url?scp=0028791694&partnerID=8YFLogxK
U2 - 10.1097/00007890-199511150-00011
DO - 10.1097/00007890-199511150-00011
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C2 - 7491698
AN - SCOPUS:0028791694
SN - 0041-1337
VL - 60
SP - 943
EP - 948
JO - Transplantation
JF - Transplantation
IS - 9
ER -