Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease.
The plasma levels of a panel of cytokines and cytokine-associated molecules (IL-1alpha, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.
Sakata
N
N
Department of Pediatrics, Osaka Medical and Research Institute for Maternal and Child Health, Japan.
Yasui
M
M
Okamura
T
T
Inoue
M
M
Yumura-Yagi
K
K
Kawa
K
K
D000208:Acute Disease; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood; D007700:Kinetics; D008297:Male; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012995:Solubility; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10