Nitric oxide formation as predictive parameter for acute graft-versus-host disease after human allogeneic bone marrow transplantation

Transplantation. 1995 Dec 15;60(11):1239-44.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Biopterin / analogs & derivatives
  • Biopterin / blood
  • Bone Marrow Transplantation / immunology*
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / diagnosis*
  • Humans
  • Interleukin-10 / blood
  • Neopterin
  • Nitrates / blood
  • Nitric Oxide / metabolism*
  • Nitrites / blood
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / metabolism
  • Solubility
  • Time Factors

Substances

  • Nitrates
  • Nitrites
  • Receptors, Tumor Necrosis Factor
  • Interleukin-10
  • Biopterin
  • Nitric Oxide
  • Neopterin