VEIN GRAFT INTIMAL HYPERPLASIA - LEUKOCYTES AND CYTOKINE GENE-EXPRESSION

Background. Intimal hyperplasia (IH), a cause of early graft failure, may be regulated by leukocyte-elaborated cytokines. We investigated le ukocyte infiltration and cytokine gene expression in vein grafts. Meth ods. Epigastric vein to femoral artery grafts were performed in Lewis rats and harvested on day 4 and weeks 1, 2, 4, 8, and 12. Neointimal a reas were measured by computerzzed planimetry. Immunoperoxidase staini ng identified for macrophapes, CD4+, CD8+, and major histocompatibilit y complex class II+ cells. Graft RNA was used in reversetranscription- polymerasc chain reaction with interleukin (IL) - 1 alpha, IL-2R, mono cyte chemoattractnnt protein-1, and transforming growth factor-beta pr imers. Results. IH was measurable at 2 weeks; the perianastomotic regi ons displayed greater IH than the midgraft (p < 0.05). MANOVA indicate d strong location (p = 0.0007) and time (p = 0.0009) effects. Immunocy tochemistry showed inflammatoryo infiltrates from 4 days to 4 ueeks; c ells were major histocompatibilily complex class II+ and primarily, mo nocytes/macrophages, with less frequent T lymphocytes (CD4+ > CD8+). I L-1 alpha messenger RNA is expressed early, disappearing after 4 weeks . Monocyte chemoattracta t protein-1 mRNA is constitutively expressed, with up-regulation at 4 days to 4 weeks. IL-2R mRNA levels fluctuate; transforming growth factor-beta is always expressed peaking at 4 days to 4 weeks. Conclusions. Gene expression of cytokines thought to modu late IH is up-regulated early in vein grafts. This coincides with graf t infiltration by activated leukocytes before and during the developme nt of IH.