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?

Pathobiology ◽  
1991 ◽  
Vol 59 (3) ◽  
pp. 171-175 ◽  
Author(s):  
E. Holler ◽  
R. Hintermeier-Knabe ◽  
H.J. Kolb ◽  
J. Kempeni ◽  
A. Möller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Clinical Correlate ◽  
Factor Alpha ◽  
Low Incidence ◽  
Necrosis Factor

scholarly journals An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin

Blood ◽  
1996 ◽  
Vol 88 (8) ◽  
pp. 3230-3239 ◽  
Author(s):  
KR Cooke ◽  
L Kobzik ◽  
TR Martin ◽  
J Brewer ◽  
J Jr Delmonte ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Idiopathic Pneumonia Syndrome ◽  
Factor Alpha ◽  
Necrosis Factor

Idiopathic pneumonia syndrome (IPS) refers to diffuse, non-infectious pneumonia that occurs after allogeneic bone marrow transplantation (BMT). We have developed a model of IPS using a well-characterized murine BMT system (B10.BR-->CBA) in which lung injury after BMT can be induced by minor histocompatibility (H) antigenic differences between donor and host. Lung pathology and broncho-alveolar lavage (BAL) fluid were analyzed in transplant recipients before and after both syngeneic and allogeneic BMT. At 2 weeks after BMT, no specific pathologic abnormalities were noted; at 6 weeks, both pneumonitis and mononuclear cell infiltration around vessels and bronchioles were observed only in mice receiving allogeneic BMT. This injury was associated with elevated BAL fluid levels of endotoxin (lipopolysaccharide [LPS]), neutrophils, and tumor necrosis factor alpha. No pathologic organisms were isolated from the respiratory tract of any animal. We also tested the role of endotoxin in the development of this injury. Injection of LPS 6 weeks after transplantation caused profound lung injury only in mice with moderate graft-versus-host disease; dramatic increases in BAL neutrophils and tumor necrosis factor alpha were observed, with alveolar hemorrhage occurring in 4 of 12 of these mice but in no other group. We conclude that (1) this murine BMT system is a potentially useful model of clinical IPS; (2) minor H differences between donor and recipient can be important stimuli in the pathogenesis of IPS; and (3) endotoxin in BAL fluid is associated with lung injury, and excess endotoxin can cause the development of alveolar hemorrhage in this model.

scholarly journals In vivo hematopoietic effects of tumor necrosis factor-alpha in normal and erythroleukemic mice: characterization and therapeutic applications

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1875-1883 ◽  
Author(s):  
CS Johnson ◽  
MJ Chang ◽  
P Furmanski
Keyword(s):  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Late Stage ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract The effects of recombinant, macrophage-derived, murine tumor necrosis factor-alpha (TNF-alpha) on hematopoiesis in vivo has been examined in normal mice and in Friend virus (FV)-induced erythroleukemic mice. Intravenous (IV) administration of a single dose of recombinant murine TNF-alpha (10(5) U per mouse) significantly suppressed normal and leukemic late-stage erythropoiesis as measured by numbers of mature erythroid colony forming cells (CFU-E) in the bone marrow and spleen and by peripheral blood reticulocyte counts. In normal animals, the immature erythroid (BFU-E), macrophage (CFU-M), and granulocyte- macrophage (CFU-GM) compartments were significantly stimulated by TNF- alpha in both the bone marrow and the spleen. In the bone marrow of leukemic mice, the BFU-E, CFU-GM, and CFU-M progenitor cell compartments were also stimulated by treatment with the monokine. In the spleens of leukemic mice (the primary site of FV leukemia cell accumulation), relative numbers of BFU-E and CFU-GM were increased by TNF-alpha, while those of CFU-M were suppressed. TNF-alpha caused a rapid decrease in the markedly elevated spleen weights of progressively leukemic mice, and in multiple doses it caused complete clinical disease regression in a significant percentage of leukemic animals. The combination of TNF-alpha with interferon-gamma (IFN-gamma) increased the incidence of leukemia regression, compared with TNF-alpha alone. These results show that TNF-alpha exerts a suppressive influence on late-stage erythropoiesis in vivo and suggest that this effect might be exploited in the treatment of acute erythroleukemia, erythroid hyperplasias, and related diseases.

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