Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation
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Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation. / Pontoppidan, Peter Erik Lotko; Jordan, Karina Kwi Im; Carlsen, Anting Liu; Uhlving, Hilde Hylland; Kielsen, Katrine; Christensen, Mette; Ifversen, Marianne R Segelcke; Nielsen, Claus Henrik; Sangild, Per Torp; Heegaard, Niels Henrik Helweg; Heilmann, Carsten; Sengeløv, Henrik; Muller, Klaus.
In: International Immunopharmacology, Vol. 25, No. 1, 03.2015, p. 180-188.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation
AU - Pontoppidan, Peter Erik Lotko
AU - Jordan, Karina Kwi Im
AU - Carlsen, Anting Liu
AU - Uhlving, Hilde Hylland
AU - Kielsen, Katrine
AU - Christensen, Mette
AU - Ifversen, Marianne R Segelcke
AU - Nielsen, Claus Henrik
AU - Sangild, Per Torp
AU - Heegaard, Niels Henrik Helweg
AU - Heilmann, Carsten
AU - Sengeløv, Henrik
AU - Muller, Klaus
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015/3
Y1 - 2015/3
N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation with significantly elevated miRNA-155 and decreased miRNA-146a levels, from day 0 to day +28 compared with pre-conditioning levels. Citrulline levels below the median at day +7 were associated with higher spontaneous production of IL-6 and TNF-α as well as higher in vitro stimulated production of IL-17A at day +21. This study is the first to demonstrate that toxic responses to chemotherapy are accompanied by differential regulation of miRNAs with opposing effects on immune regulation. We find that a proinflammatory miRNA profile is sustained during the first three weeks after the transplantation, indicating that these miRNAs may play a role in the regulation of the inflammatory environment during immune reconstitution after HSCT.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation with significantly elevated miRNA-155 and decreased miRNA-146a levels, from day 0 to day +28 compared with pre-conditioning levels. Citrulline levels below the median at day +7 were associated with higher spontaneous production of IL-6 and TNF-α as well as higher in vitro stimulated production of IL-17A at day +21. This study is the first to demonstrate that toxic responses to chemotherapy are accompanied by differential regulation of miRNAs with opposing effects on immune regulation. We find that a proinflammatory miRNA profile is sustained during the first three weeks after the transplantation, indicating that these miRNAs may play a role in the regulation of the inflammatory environment during immune reconstitution after HSCT.
KW - Adolescent
KW - Adult
KW - Biomarkers
KW - Cells, Cultured
KW - Child
KW - Child, Preschool
KW - Citrulline
KW - Cytokines
KW - Denmark
KW - Drug Therapy
KW - Enterocytes
KW - Gene Expression Regulation
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Infant
KW - Inflammation Mediators
KW - Intestines
KW - Leukocytes, Mononuclear
KW - Lymphocyte Activation
KW - Male
KW - MicroRNAs
KW - Middle Aged
KW - Myeloablative Agonists
KW - Prospective Studies
KW - Transplantation Conditioning
KW - Young Adult
U2 - 10.1016/j.intimp.2014.12.038
DO - 10.1016/j.intimp.2014.12.038
M3 - Journal article
C2 - 25614225
VL - 25
SP - 180
EP - 188
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 1
ER -
ID: 160609759