PMID- 11798503
OWN - NLM
STAT- MEDLINE
DCOM- 20030411
LR  - 20231213
IS  - 1525-8165 (Print)
IS  - 1525-8165 (Linking)
VI  - 10
IP  - 6
DP  - 2001 Dec
TI  - Interleukin-18 binding protein in acute graft versus host disease and engraftment 
      following allogeneic peripheral blood stem cell transplants.
PG  - 769-76
AB  - Dysregulation of the cytokine network plays an important role in 
      graft-versus-host disease (GVHD). Interleukin-18 (IL-18) is an obligatory 
      cytokine for interferon-gamma (IFN-gamma) production and IFN-gamma and 
      sIFN-gammaR are elevated in patients with GVHD. Because IL-18 binding protein 
      (IL-18BP) is an inhibitor of IL-18-mediated IFN-gamma production, we evaluated 
      IL-18BP levels in patients undergoing allogeneic peripheral blood stem cell 
      transplantation (PBSCT). IL-18BP levels were assessed in 14 patients on day -10 
      (before conditioning), on the day of transplant, on the day of engraftment, and 
      during transplant-related complications. A comparison of the kinetics of IL-18BP 
      and soluble(s) IL-6R, sIFN-gammaR, IL-18 serum levels was performed. IL-18BP 
      levels were assessed by specific monoclonal antibodies in a double-sandwich 
      enzyme-linked immunosorbent assay (ELISA). In all patients IL-18BP levels 
      decreased during conditioning and increased in parallel with engraftment (p < 
      0.05). Accordingly, during rejection, IL-18BP serum levels remained low and 
      similar to pretransplant levels. The mean elevation of IL-18BP detected in 
      association to acute GVHD was significantly higher in comparison to normal 
      engraftment (p < 0.05). A correlation between IL-18BP, sIFNgammaR, and sIL-6R 
      serum levels was found in all patients. No correlation between IL-18 and IL-18BP 
      serum levels was found in patients undergoing uneventful PBSCT and rejection, 
      whereas a marked increase in both IL-18 and IL-18BP levels was detected during 
      acute GVHD (p < 0.01). Our data suggest that the dysregulation of IL-18 and 
      IL-18BP may be important in the pathophysiology of transplant-related 
      complications. Furthermore, because preliminary data from our group show that 
      IL-18 blockage ameliorates GVHD in murine models, it is inferred that these 
      cytokines may represent potential targets in the development of new therapeutic 
      strategies in acute GVHD.
FAU - Zecchina, G
AU  - Zecchina G
AD  - Department of Scienze Cliniche e Biologiche Universita di Torino, Italy.
FAU - Novick, D
AU  - Novick D
FAU - Rubinstein, M
AU  - Rubinstein M
FAU - Barak, V
AU  - Barak V
FAU - Dinarello, C
AU  - Dinarello C
FAU - Nagler, A
AU  - Nagler A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Hematother Stem Cell Res
JT  - Journal of hematotherapy & stem cell research
JID - 100892915
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (Receptors, Interferon)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Glycoproteins/*blood
MH  - Graft Survival/*immunology
MH  - Graft vs Host Disease/blood/*etiology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Interleukin-18/blood
MH  - Male
MH  - Middle Aged
MH  - Receptors, Interferon/blood
MH  - Receptors, Interleukin-6/blood
MH  - Stem Cell Transplantation/*adverse effects
MH  - Transplantation Conditioning
MH  - Transplantation, Homologous
MH  - Interferon gamma Receptor
EDAT- 2002/01/19 10:00
MHDA- 2003/04/12 05:00
CRDT- 2002/01/19 10:00
PHST- 2002/01/19 10:00 [pubmed]
PHST- 2003/04/12 05:00 [medline]
PHST- 2002/01/19 10:00 [entrez]
AID - 10.1089/152581601317210863 [doi]
PST - ppublish
SO  - J Hematother Stem Cell Res. 2001 Dec;10(6):769-76. doi: 
      10.1089/152581601317210863.