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 in volved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL-6-related cytokines in chronic CHF in humans by analysi ng 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 docum ented in myocardial samples using cDNA array hybridization and RNase protec tion assays. Immunohistochemistry was used to detect leukaemia inhibitory f actor (LIF), IL-6 and glycoprotein 130 (gp130) in myocardial tissues. Results Myocardial gene activity was documented for the majority of IL-6 fa mily cytokines and their receptors. Immunohistochemical analysis localized IL-6, LIF and their common receptor subunit gp 130 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 gp 130 m RNA levels were not statistically different between patients and donors, bu t in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels w ere significantly higher in left atrium compared with left ventricle in bot h patients and donors. Conclusions Both mRNA and proteins of gp130 and its ligands IL-6 and LIF ar e expressed in both nonfailing and failing human myocardium. The elevated L IF mRNA levels in left ventricles from patients with end-stage heart failur e suggest a role for LIF in the pathogenesis of CHF.