Impairment of GM-CSF production in myelodysplastic syndromes

Br J Haematol. 1993 Jun;84(2):227-31. doi: 10.1111/j.1365-2141.1993.tb03056.x.

Abstract

In this study we evaluated the production of granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) by enriched bone marrow (BM) macrophages in 15 patients affected by myelodysplasia and 20 normal BM donors. The presence of GM-CSF, IL-6 and TNF-alpha in the culture supernatants of BM macrophages was detectable only after stimulation with lipopolysaccharide (LPS), whereas no differences were present in the amount of IL-6 and TNF-alpha between myelodysplastic patients and normal controls, GM-CSF production appeared eight-fold reduced in BM macrophage culture supernatants from myelodysplastic patients with respect to normal controls. After further experiments, we concluded that the impaired release of GM-CSF by BM macrophages could not be due to a different production kinetic in myelodysplastic patients. Moreover, the number of multipotent (CFU-GEMM), granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitors was significantly impaired in myelodysplastic patients. In conclusion, we demonstrated that the production of GM-CSF by purified adherent cells from MDS patients is markedly impaired in spite of the peripheral blood cytopenia. This selective defect in GM-CSF production, along with an intrinsic defect of haematopoietic progenitor cells, might contribute to the impairment of haematopoiesis always observed in myelodysplastic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / immunology*
  • Cell Adhesion
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Humans
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor