Low incidence of transplant-related complications in patients with chronic release of tumor necrosis factor-alpha before admission to bone marrow transplantation: a clinical correlate of cytokine desensitization?
To investigate the role of tumor necrosis factor-alpha (TNF-alpha) released by activated macrophages, sequential serum samples of 120 patients undergoing bone marrow transplantation (BMT) were analyzed by enzyme-linked immunosorbent assay. De novo increases in serum TNF-alpha levels were correlated with the development of acute endothelial complications as well as acute graft-versus-host disease. In addition, the analysis of time courses revealed a different capacity of TNF-alpha regulation at various phases of BMT. While patients with acute TNF-alpha release in the first 2 weeks of BMT had a significantly enhanced incidence of complications, a subgroup of 9 patients with chronic asymptomatic release of TNF-alpha before admission to BMT was observed. These patients were protected from complications in the course of the first 6 months of BMT. Our observations indicate the occurrence of desensitization for TNF-alpha, as it is also reported after repeated injections of TNF-alpha or endotoxin in experimental models.
Holler
E
E
Institut für klinische Hämatologie der GSF.
Hintermeier-Knabe
R
R
Kolb
H J
HJ
Kempeni
J
J
Möller
A
A
Liesenfeld
S
S
Daum
L
L
Wilmanns
W
W
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha