Tumour necrosis factor-alpha expression in idiopathic dilated cardiomyopathy: correlation to myocardial inflammatory activity.
High numbers of inflammatory cells are found in a subgroup of patients with idiopathic dilated cardiomyopathy (IDCM). We hypothesized that the extent of inflammation is linked to myocardial TNF-alpha expression in human IDCM. Fourteen patients who consecutively underwent endomyocardial biopsy (EMB) were stratified into two groups-a group with low and a group with high myocardial inflammatory index (MII)-based on immunohistochemical analysis of cellular infiltration and HLA I and II expression. Myocardial TNF-alpha messenger RNA (mRNA) expression was determined by reverse transcriptase polymerase chain reaction, TNF-alpha protein was localized by immunohistochemistry and TNF-alpha serum levels were measured by EIA. IDCM patients with a high MII (n=6) showed a 1. 9-fold higher TNF-alpha mRNA expression when compared to IDCM patients with low MII (n=8, P=0.020). TNF-alpha protein was detected at perinuclear regions of cardiac myocytes and the endothelium. TNF-alpha serum levels were 3.0 (0.55) pg/ml in patients with high MII compared to 1.35 (0.20) pg/ml in patients with low MII (P=0.017). According to immunolocalization cardiac myocytes and the endothelium seem to be the major source of TNF-alpha production. Whether the elevated systemic level of TNF-alpha found in patients with high MII are elaborated by the myocardium or are produced by other tissues representing a general immune activation is not clear.
Sigusch
H H
HH
Department of Internal Medicine, Division of Cardiology, University of Jena, Jena, Germany. Holger.Sigusch@uni-jena.de
Lehmann
M H
MH
Schnittler
U
U
Reinhardt
D
D
Figulla
H R
HR
D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha