Article

Cytokine and chemokine patterns across one hundred days following hematopoietic stem cell transplantation in children.

Associate Professor of Pediatrics (Critical Care Medicine), Children's Hospital Los Angeles. Electronic address: .
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.15). 12/2013; DOI: 10.1016/j.bbmt.2013.11.026
Source: PubMed

ABSTRACT We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT) by assaying fifty-one cytokines and chemokines (Luminex multiplex cytokine kits, Panomics/Affymetrix, Santa Clara, CA) each week for one hundred days in fifty-one children receiving allogeneic (n=44) or autologous HSCT (n=7). Assay values were reported as mean fluorescence intensity (MFI). Log transformation converted MFI to clinically relevant measures (i.e., picograms/mL). We searched for potential markers of transplant complications by employing mixed treatment by subjects ANOVA (analysis of variance). Global cytokine secretion in HSCT recipients was significantly lower than in concurrent control patients (n=11). Coincident with the nadir in white blood cell count, the concentration of many cytokines declined further by the second and third week: CD40, FGF-β, ICAM1, IL-1α, IL-1β, IL-2, IL-5, IL-4, IL-7, IL-12P40, IL-12P70, IL-13, IL-15, IL-17, interferon, IP-10, MCP3, MIG, MIP1β, NGF, PAI1, PDGFBB, RANTES, resistin, sFAS ligand, TNF-α, TGF-α, TGF-β, TRAIL, VCAM1. All of these analytes (except MIG) subsequently rebounded by week 4 (coincident with engraftment and recovery of the white blood cell count), but often still remained well below the control levels. Concurrent with the collective nadir of multiple cytokines, MCP-1, GRO-α and leptin surged during weeks 2-4. High levels of leptin persisted throughout the one hundred post-transplant days. Also during weeks 2-4, hepatocyte growth factor (HGF) and interleukin-6 (IL-6) surged in children with complications, but not in those without complications. The peak in HGF was more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at least two weeks prior to the clinical diagnosis of VOD or graft-vs-host disease (GVHD). From week 4 onwards in all groups, the MFI of the cytokine resistin increased to 5-15 times above concurrent control. Hepatocyte growth factor has now emerged in three or more biomarker discovery efforts for GVHD (and in our population, for VOD as well). Hepatocyte growth factor (with or without IL-6) should be investigated as a potential predictive biomarker of VOD or GVHD. Alternatively, the hyper-inflammatory 'signature' provided by a multi-cytokine assay may be predictive.

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