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.
Weiss
G
G
Department for Internal Medicine, University Hospital, Innsbruck, Austria.
Schwaighofer
H
H
Herold
M
M
Nachbaur
D
D
Wachter
H
H
Niederwieser
D
D
Werner
E R
ER
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