Clinical "cytokine storm" as revealed by monocyte intracellular flow cytometry: Correlation of tumor necrosis factor α with severe gut graft-versus-host disease

Daniel H. Fowler, Jason Foley, Jeannie Whit Shan Hou, Jeanne Odom, Kate Castro, Seth M. Steinberg, Juan Gea-Banacloche, Claude Sportes, Ronald E. Gress, Michael R. Bishop

Research output: Contribution to journalArticle

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Abstract

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 1α (IL-1α) and tumor necrosis factor α (TNF-α) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1α and TNF-α 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-1α and TNF-α 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-1α 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-α 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-α level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-α 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-1α, followed by TNF-α. Serial measurement of monocyte cytokines, in particular, TNF-α, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalClinical Gastroenterology and Hepatology
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2004

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Graft vs Host Disease
Monocytes
Flow Cytometry
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-1
Hematopoietic Stem Cell Transplantation
Hematologic Neoplasms
Cyclosporine
Siblings
Macrophages

Keywords

  • CSA
  • Cyclosporine A
  • FITC
  • Fluorescein isothiocyanate
  • GVHD
  • Graft-versus-host disease
  • HSCT
  • Hematopoietic stem-cell transplantation
  • IC-FCM
  • IL-1α
  • IV
  • Interleukin 1α
  • Intracellular flow cytometry
  • Intravenously
  • TNF-α

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Clinical "cytokine storm" as revealed by monocyte intracellular flow cytometry : Correlation of tumor necrosis factor α with severe gut graft-versus-host disease. / Fowler, Daniel H.; Foley, Jason; Hou, Jeannie Whit Shan; Odom, Jeanne; Castro, Kate; Steinberg, Seth M.; Gea-Banacloche, Juan; Sportes, Claude; Gress, Ronald E.; Bishop, Michael R.

In: Clinical Gastroenterology and Hepatology, Vol. 2, No. 3, 01.03.2004, p. 237-245.

Research output: Contribution to journalArticle

Fowler, Daniel H. ; Foley, Jason ; Hou, Jeannie Whit Shan ; Odom, Jeanne ; Castro, Kate ; Steinberg, Seth M. ; Gea-Banacloche, Juan ; Sportes, Claude ; Gress, Ronald E. ; Bishop, Michael R. / Clinical "cytokine storm" as revealed by monocyte intracellular flow cytometry : Correlation of tumor necrosis factor α with severe gut graft-versus-host disease. In: Clinical Gastroenterology and Hepatology. 2004 ; Vol. 2, No. 3. pp. 237-245.
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abstract = "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 1α (IL-1α) and tumor necrosis factor α (TNF-α) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1α and TNF-α 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-1α and TNF-α 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-1α 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-α 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-α level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-α 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-1α, followed by TNF-α. Serial measurement of monocyte cytokines, in particular, TNF-α, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.",
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T1 - Clinical "cytokine storm" as revealed by monocyte intracellular flow cytometry

T2 - Correlation of tumor necrosis factor α with severe gut graft-versus-host disease

AU - Fowler, Daniel H.

AU - Foley, Jason

AU - Hou, Jeannie Whit Shan

AU - Odom, Jeanne

AU - Castro, Kate

AU - Steinberg, Seth M.

AU - Gea-Banacloche, Juan

AU - Sportes, Claude

AU - Gress, Ronald E.

AU - Bishop, Michael R.

PY - 2004/3/1

Y1 - 2004/3/1

N2 - 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 1α (IL-1α) and tumor necrosis factor α (TNF-α) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1α and TNF-α 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-1α and TNF-α 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-1α 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-α 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-α level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-α 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-1α, followed by TNF-α. Serial measurement of monocyte cytokines, in particular, TNF-α, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.

AB - 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 1α (IL-1α) and tumor necrosis factor α (TNF-α) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1α and TNF-α 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-1α and TNF-α 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-1α 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-α 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-α level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-α 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-1α, followed by TNF-α. Serial measurement of monocyte cytokines, in particular, TNF-α, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies.

KW - CSA

KW - Cyclosporine A

KW - FITC

KW - Fluorescein isothiocyanate

KW - GVHD

KW - Graft-versus-host disease

KW - HSCT

KW - Hematopoietic stem-cell transplantation

KW - IC-FCM

KW - IL-1α

KW - IV

KW - Interleukin 1α

KW - Intracellular flow cytometry

KW - Intravenously

KW - TNF-α

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