The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure.
BACKGROUND
Activation of the endotoxin (LPS) receptor, CD14, leads to tumor necrosis factor-alpha (TNF) production. Plasma LPS activity is elevated in patients with severe chronic heart failure (CHF). An anti-CD14 antibody, IC14, blocks TNF production in healthy volunteers. It is not known whether IC14 prevents TNF production in CHF patients.


RESULTS
Blood from 20 CHF patients (age 64+/-2.1 years, NYHA class 2.2+/-0.1, LVEF 27+/-3%, mean+/-SEM) was pre-incubated with 0.5, 1.0, 5.0, 10 and 50 microg/mL IC14 for 1 h followed by incubation with 1 or 10 ng/mL LPS for 6 h. Fourteen subjects served as controls (58+/-2.4 years). LPS-stimulated TNF release was 76% and 60% greater at 1 and 10 ng/mL LPS, respectively, in CHF patients versus controls (p=0.07 and p=0.008). IC14 at concentrations of 5.0, 10 and 50 microg/mL substantially reduced TNF production in response to stimulation with LPS (all p<0.05). CD14 receptor density was similar in patients and controls. In controls, but not in CHF patients, there was a positive correlation between CD14 receptor density and TNF production (r=0.61, p=0.03).


CONCLUSIONS
IC14 suppresses LPS-stimulated whole blood TNF production in patients with CHF and in normal subjects and therefore may represent a novel therapeutic strategy for CHF patients with systemic immune activation.
Genth-Zotz
Sabine
S
Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, UK. genth@2-med.klinik.uni-mainz.de
von Haehling
Stephan
S
Bolger
Aidan P
AP
Kalra
Paul R
PR
Wensel
Roland
R
Coats
Andrew J S
AJ
Volk
Hans-Dieter
HD
Anker
Stefan D
SD
D000368:Aged; D002303:Cardiac Output, Low / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha