BACKGROUND & AIMS: Gut graft-versus-host disease (GVHD) contributes significantly to lethality after allogeneic hematopoietic stem-cell transplantation (HSCT). In murine models, macrophage secretion of interleukin 1alpha (IL-1alpha) and tumor necrosis factor alpha (TNF-alpha) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1alpha and TNF-alpha production were evaluated after HSCT. METHODS: Patients with refractory hematologic malignancy (n = 17) underwent reduced-intensity conditioning, HLA-matched sibling HSCT, and cyclosporine A GVHD prophylaxis. After HSCT, monocyte IL-1alpha and TNF-alpha levels were measured using intracellular flow cytometry (IC-FCM), and results were correlated with clinical GVHD. RESULTS: Incidences of acute GVHD were none (n = 3), grades I-II (n = 9), or grades III-IV (n = 5; each case with stage 2-3 gut GVHD). Posttransplantation monocyte IL-1alpha production (percentage of CD14(+)IL-1(+) cells) increased significantly from 8.7% +/- 3.7% (week 2) to 40.3% +/- 7.3% (week 4; P = 0.0065) and was not associated with GVHD severity (P = 1.00). Conversely, increases in monocyte TNF-alpha were quantitatively reduced and temporally delayed, from 0.6% +/- 0.2% (week 2) to 3.6% +/- 1.4% (week 6; P = 0.076). Most importantly, elevation of monocyte TNF-alpha level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-alpha levels typically preceded the onset of gut GVHD symptoms. CONCLUSIONS: Human gut GVHD after reduced-intensity allogeneic HSCT is associated with monocyte cytokine secretion initially involving IL-1alpha, followed by TNF-alpha. Serial measurement of monocyte cytokines, in particular, TNF-alpha, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.
BACKGROUND & AIMS: Gut graft-versus-host disease (GVHD) contributes significantly to lethality after allogeneic hematopoietic stem-cell transplantation (HSCT). In murine models, macrophage secretion of interleukin 1alpha (IL-1alpha) and tumor necrosis factor alpha (TNF-alpha) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1alpha and TNF-alpha production were evaluated after HSCT. METHODS:Patients with refractory hematologic malignancy (n = 17) underwent reduced-intensity conditioning, HLA-matched sibling HSCT, and cyclosporine AGVHD prophylaxis. After HSCT, monocyte IL-1alpha and TNF-alpha levels were measured using intracellular flow cytometry (IC-FCM), and results were correlated with clinical GVHD. RESULTS: Incidences of acute GVHD were none (n = 3), grades I-II (n = 9), or grades III-IV (n = 5; each case with stage 2-3 gut GVHD). Posttransplantation monocyte IL-1alpha production (percentage of CD14(+)IL-1(+) cells) increased significantly from 8.7% +/- 3.7% (week 2) to 40.3% +/- 7.3% (week 4; P = 0.0065) and was not associated with GVHD severity (P = 1.00). Conversely, increases in monocyte TNF-alpha were quantitatively reduced and temporally delayed, from 0.6% +/- 0.2% (week 2) to 3.6% +/- 1.4% (week 6; P = 0.076). Most importantly, elevation of monocyte TNF-alpha level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-alpha levels typically preceded the onset of gut GVHD symptoms. CONCLUSIONS:Human gut GVHD after reduced-intensity allogeneic HSCT is associated with monocyte cytokine secretion initially involving IL-1alpha, followed by TNF-alpha. Serial measurement of monocyte cytokines, in particular, TNF-alpha, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.
Authors: Chrystal M Paulos; Andrew Kaiser; Claudia Wrzesinski; Christian S Hinrichs; Lydie Cassard; Andrea Boni; Pawel Muranski; Luis Sanchez-Perez; Douglas C Palmer; Zhiya Yu; Paul A Antony; Luca Gattinoni; Steven A Rosenberg; Nicholas P Restifo Journal: Clin Cancer Res Date: 2007-09-15 Impact factor: 12.531
Authors: Riham El-Asady; Rongwen Yuan; Kechang Liu; Donghua Wang; Ronald E Gress; Philip J Lucas; Cinthia B Drachenberg; Gregg A Hadley Journal: J Exp Med Date: 2005-05-16 Impact factor: 14.307