Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.
BACKGROUND
Studies in different animal models and plasma analyses in humans suggest that members of the interleukin-6 (IL-6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL-6-related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end-stage heart failure and donor hearts.


METHODS
Gene expression of cytokines/receptors of the IL-6 family was documented in myocardial samples using cDNA array hybridization and RNase protection assays. Immunohistochemistry was used to detect leukaemia inhibitory factor (LIF), IL-6 and glycoprotein 130 (gp130) in myocardial tissues.


RESULTS
Myocardial gene activity was documented for the majority of IL-6 family cytokines and their receptors. Immunohistochemical analysis localized IL-6, LIF and their common receptor subunit gp130 to myocytes and vascular smooth muscle cells. LIF mRNA levels were enhanced in the left ventricles of CHF patients relative to the left ventricles of donor hearts (patients 4.6 +/- 4.7 vs. donors 0.3 +/- 0.3, P < 0.005). Myocardial IL-6 and gp130 mRNA levels were not statistically different between patients and donors, but in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels were significantly higher in left atrium compared with left ventricle in both patients and donors.


CONCLUSIONS
Both mRNA and proteins of gp130 and its ligands IL-6 and LIF are expressed in both nonfailing and failing human myocardium. The elevated LIF mRNA levels in left ventricles from patients with end-stage heart failure suggest a role for LIF in the pathogenesis of CHF.
Eiken
H G
HG
University of Oslo, The National Hospital, Ullevål Hospital Oslo, Norway. h.g.eiken@klinmed.uio.no
Øie
E
E
Damås
J K
JK
Yndestad
A
A
Bjerkeli
V
V
Aass
H
H
Simonsen
S
S
Geiran
O R
OR
Tønnessen
T
T
Christensen
G
G
Frøland
S S
SS
Gullestad
L
L
Attramadal
H
H
Aukrust
P
P
D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D002908:Chronic Disease; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics*; D006333:Heart Failure / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050822:Cytokine Receptor gp130; D012260:Ribonucleases