Serum cytokine concentrations and acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation

Concurrent measurement of ten cytokines and their respective ratios using cytometric bead array

Nobuharu Fujii, Akio Hiraki, Keisuke Aoe, Tomoyuki Murakami, Kazuma Ikeda, Kozo Masuda, Keitaro Matsuo, Katsuji Shinagawa, Fumihiko Ishimaru, Kazuro Sugi, Zbigniew Darzynkiewicz, Mitsune Tanimoto

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Both inflammatory and anti-inflammatory cytokines have been reported to be associated with acute graft-versus-host disease (aGVHD). However, their role and possible mutual interactions during aGVHD are not well understood. Eight patients with aGVHD and eight without who had undergone allogeneic HLA-identical peripheral blood stem cell transplantation were studied. The patients had no other complications known to affect serum concentration of cytokines, including infection. Serum concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ were concurrently measured by a new technique, the cytometric bead array (CBA). We found that serum concentrations of IL-5, IL-6 and IL-10 were significantly higher in patients with aGVHD than in patients without it. By ratiometric analysis, the ratios of IL-5/IL-2, IL-5/IL-4, IL-6/ IL-4 in patients with aGVHD were increased compared to the patients with no evidence of aGVHD. ROC analysis demonstrated that the ratio of IL-5/IL-4 was the most sensitive parameter associated with aGVHD. The second best marker of aGVHD was increased IL-5 concentration. Thus, our results indicate that the ratio of a particular cytokine/ cytokine could be a potential diagnostic marker for aGVHD, more sensitive that the serum level of a given cytokine. This observation is consistent with a cross-talk among some cytokines and their possible interactions via respective receptors on cytokine-producing cells; these interactions may play an important role in pathogenesis of aGVHD. Further studies including a large number of patients and concurrent measurement of a variety of cytokines are needed to fully assess the diagnostic value of the cytokine ratiometric analysis. The CBA methodology provides a convenient and useful tool in such studies.

Original languageEnglish
Pages (from-to)881-885
Number of pages5
JournalInternational Journal of Molecular Medicine
Volume17
Issue number5
Publication statusPublished - May 2006

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Peripheral Blood Stem Cell Transplantation
Graft vs Host Disease
Cytokines
Interleukin-5
Serum
Interleukin-4
Interleukin-6
Interleukin-10
Interleukin-2
Cytokine Receptors
Interleukin-8
Interleukin-1
ROC Curve
Anti-Inflammatory Agents

Keywords

  • Diagnostic marker
  • Flow cytometry

ASJC Scopus subject areas

  • Genetics

Cite this

Serum cytokine concentrations and acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation : Concurrent measurement of ten cytokines and their respective ratios using cytometric bead array. / Fujii, Nobuharu; Hiraki, Akio; Aoe, Keisuke; Murakami, Tomoyuki; Ikeda, Kazuma; Masuda, Kozo; Matsuo, Keitaro; Shinagawa, Katsuji; Ishimaru, Fumihiko; Sugi, Kazuro; Darzynkiewicz, Zbigniew; Tanimoto, Mitsune.

In: International Journal of Molecular Medicine, Vol. 17, No. 5, 05.2006, p. 881-885.

Research output: Contribution to journalArticle

Fujii, Nobuharu ; Hiraki, Akio ; Aoe, Keisuke ; Murakami, Tomoyuki ; Ikeda, Kazuma ; Masuda, Kozo ; Matsuo, Keitaro ; Shinagawa, Katsuji ; Ishimaru, Fumihiko ; Sugi, Kazuro ; Darzynkiewicz, Zbigniew ; Tanimoto, Mitsune. / Serum cytokine concentrations and acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation : Concurrent measurement of ten cytokines and their respective ratios using cytometric bead array. In: International Journal of Molecular Medicine. 2006 ; Vol. 17, No. 5. pp. 881-885.
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AU - Ikeda, Kazuma

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AU - Matsuo, Keitaro

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