title: 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.
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-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha and IFN-gamma 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.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School, Okayama, Japan.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujii
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Murakami
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kozo
authors.initials: K
authors.lastname: Masuda
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shinagawa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishimaru
authors.forename: Kazuro
authors.initials: K
authors.lastname: Sugi
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Darzynkiewicz
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D005260:Female; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012372:ROC Curve; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4