PMID- 30316805
OWN - NLM
STAT- MEDLINE
DCOM- 20190326
LR  - 20200309
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 69
DP  - 2019 Jan
TI  - Interleukin-18 plays a dispensable role in murine and likely also human bone 
      marrow failure.
PG  - 54-64.e2
LID - S0301-472X(18)30861-0 [pii]
LID - 10.1016/j.exphem.2018.10.003 [doi]
AB  - Interleukin-18 (IL-18), also known as interferon-gamma (IFN-gamma)-inducing factor, 
      is involved in Th1 responses and regulation of immunity. Accumulating evidence 
      implicates IL-18 in autoimmune diseases, but little is known of its role in 
      acquired aplastic anemia (AA), the immune-mediated destruction of bone marrow 
      (BM) hematopoietic stem and progenitor cells (HSPCs). IL-18 protein levels were 
      significantly elevated in sera of severe AA (SAA) patients, including both 
      responders and nonresponders assayed before treatment, and decreased after 
      treatment. IL-18 receptor (IL-18R) was expressed on HSPCs. Co-culture of human BM 
      CD34(+) cells from healthy donors with IL-18 upregulated genes in the helper 
      T-cell and Notch signaling pathways and downregulated genes in the cell cycle 
      regulation, telomerase, and IL-6 signaling pathways. Plasma IL-18 levels were 
      also elevated in murine models of immune-mediated BM failure. However, deletion 
      of IL-18 in donor lymph node cells or deletions of either IL-18 or IL-18R in 
      recipients did not attenuate elevations of circulating IFN-gamma, tumor necrosis 
      factor-alpha, or IL-6, nor did they alleviate BM failure. In summary, our 
      findings suggest that, although increased circulating IL-18 is a feature of SAA, 
      it may reflect an aberrant immune response but be dispensable to the pathogenesis 
      of AA.
CI  - Published by Elsevier Inc.
FAU - Wu, Zhijie
AU  - Wu Z
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Giudice, Valentina
AU  - Giudice V
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Chen, Jichun
AU  - Chen J
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Sun, Wanling
AU  - Sun W
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Lin, Zenghua
AU  - Lin Z
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Keyvanfar, Keyvan
AU  - Keyvanfar K
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Talasani, Nidhi
AU  - Talasani N
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Kajigaya, Sachiko
AU  - Kajigaya S
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Feng, Xingmin
AU  - Feng X
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA. Electronic address: fengx2@nhlbi.nih.gov.
FAU - Young, Neal S
AU  - Young NS
AD  - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
LA  - eng
GR  - Z01 HL002315-21/Intramural NIH HHS/United States
GR  - Z01 HL002315-22/Intramural NIH HHS/United States
GR  - Z01 HL002315-23/Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20181012
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (IFNG protein, human)
RN  - 0 (IFNG protein, mouse)
RN  - 0 (IL18R1 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Il18r1 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-6, mouse)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia, Aplastic/genetics/*immunology/pathology
MH  - Animals
MH  - Child
MH  - Child, Preschool
MH  - Disease Models, Animal
MH  - Female
MH  - Hematopoietic Stem Cells/*metabolism/pathology
MH  - Humans
MH  - Interferon-gamma/genetics/immunology
MH  - Interleukin-18/genetics/*immunology
MH  - Interleukin-18 Receptor alpha Subunit/genetics/immunology
MH  - Interleukin-6/genetics/immunology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - T-Lymphocytes, Helper-Inducer/immunology/pathology
MH  - Tumor Necrosis Factor-alpha/genetics/immunology
PMC - PMC6309608
MID - NIHMS1509494
COIS- Conflicts of Interest Disclosures The authors declare no competing financial 
      interests.
EDAT- 2018/10/15 06:00
MHDA- 2019/03/27 06:00
PMCR- 2020/01/01
CRDT- 2018/10/15 06:00
PHST- 2018/07/13 00:00 [received]
PHST- 2018/10/06 00:00 [revised]
PHST- 2018/10/08 00:00 [accepted]
PHST- 2018/10/15 06:00 [pubmed]
PHST- 2019/03/27 06:00 [medline]
PHST- 2018/10/15 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - S0301-472X(18)30861-0 [pii]
AID - 10.1016/j.exphem.2018.10.003 [doi]
PST - ppublish
SO  - Exp Hematol. 2019 Jan;69:54-64.e2. doi: 10.1016/j.exphem.2018.10.003. Epub 2018 
      Oct 12.