Cross talk between inflammatory cytokines and granulocyte-macrophage colony-stimulating factor in transplant vasculopathy.

BACKGROUND: Transplant vasculopathy limits the clinical results of solid organ transplantation.

MATERIALS AND METHODS: Thirty-three arterial grafts were implanted in the abdominal aorta of Lewis rats. The animals were humanely sacrificed 4 wk after surgery. The study groups had 15 arterial isografts and 18 arterial allografts. Growth factors and inflammatory cytokines, released by the removed grafts, were studied in organ culture. The released growth factors were analyzed in vitro to assess their effect on the proliferation of endothelial, smooth muscle cells and fibroblasts.

RESULTS: In arterial isogenic and allogenic grafts, platelet-derived growth factor and basic fibroblastic growth factor release was minimal (P < 0.01). There was a significant release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α (TNF-α; P < 0.001) in allografts. GM-CSF and TNF-α, at concentrations in the allograft organ cultures, stimulated significantly the growth of smooth muscle cells. The simultaneous action of TNF-α and GM-CSF had an exponential growth effect on endothelial cells and smooth muscle cells. Interleukin (IL)-1, IL-2, and IL-9 were released in high quantities by allografts. In vitro, IL-1, IL-2, and IL-9 facilitated the growth effect of GM-CSF and TNF-α.

CONCLUSIONS: Transplant vasculopathy depends on the simultaneous and complementary additive effects of several growth factors and cytokines, which have a continuous "cross talk."