Nitric oxide formation as predictive parameter for acute graft-versus-host disease after human allogeneic bone marrow transplantation.
Due to the accumulation of evidence concerning a putative role of nitric oxide (NO) in graft-versus-host disease (GVHD), we performed follow-up measurements of the stable end-products of NO, nitrite/nitrate (NO2-/NO3-) in plasma of patients undergoing allogeneic (n = 16) and autologous (n = 6, as a control) bone marrow transplantation. NO2-/NO3- concentrations were set in relation to the clinical course and to serum levels of soluble tumor necrosis factor receptor 75 (sT-NFrec 75) and neopterin, both of which are known to be sensitive indicators of cellular immune activation phenomena involving macrophages in vivo, and endogenous interleukin (IL)-10, a major T helper cell type 2 (TH-2)-derived cytokine and potent inhibitor of macrophage activation and NO formation. A significant rise of NO2-/NO3- levels was observed in patients with GVHD and preceded the onset of clinical symptoms by up to 3 days. In contrast to indicators of macrophage activation, i.e., neopterin and sT-NFrec75, NO2-/NO3- concentrations were not significantly altered from baseline levels during infectious complications, as NO2-/NO3- concentrations did not fluctuate in patients after autologous engraftment. During episodes of acute GVHD, NO2-/NO3- concentrations showed a strong positive correlation with levels of plasma neopterin and sTNFrec 75, but were also significantly related to IL-10. In non-GVHD patients, a negative correlation between IL-10 and NO2-/NO3- concentrations was evident. Therefore, NO2-/NO3- determination may be a valuable early indicator of the initiation of human GVHD. Our results provide some further insights concerning cytokine-related metabolic changes in the course of human GVHD in vivo which may prove useful in the development of new therapeutic approaches for this disease.
Department for Internal Medicine, University Hospital, Innsbruck, Austria.
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G
Weiss
H
H
Schwaighofer
M
M
Herold
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D
Nachbaur
H
H
Wachter
D
D
Niederwieser
E R
ER
Werner
D000208:Acute Disease; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D019798:Neopterin; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013997:Time Factors
D009566:Nitrates; D009573:Nitrites; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D001708:Biopterins; D009569:Nitric Oxide; D019798:Neopterin