Relationship between interleukin-6 production in the lungs and pulmonary vascular resistance in patients with congestive heart failure.
OBJECTIVE
We evaluated whether interleukin (IL)-6 is produced in the pulmonary circulation and investigated the relationship between IL-6 spillover in the lung and pulmonary vascular resistance (PVR) in patients with congestive heart failure (CHF).


METHODS
Blood samples were obtained from the main pulmonary artery and pulmonary capillary wedge region in 50 patients with symptomatic left ventricular dysfunction, who had undergone cardiac catheterization, and 9 age-matched control subjects. Plasma IL-6, tumor necrosis factor-alpha, norepinephrine (NE), endothelin-1, atrial and brain natriuretic peptide, and cyclic guanosine monophosphate (cGMP) levels were determined.


RESULTS
Plasma IL-6 concentrations were significantly higher in the pulmonary capillary wedge region than in the main pulmonary artery in both control subjects and patients with CHF. IL-6 production in the lung increased markedly in patients with severe CHF compared with control subjects and patients with mild CHF. Among hemodynamic variables, neurohumoral factors, and medications, plasma NE levels (p < 0.0001) showed an independent and significant positive relationship with IL-6 production in the lung, and treatment with beta-blockers (p = 0.004) showed an independent and significant negative relationship with IL-6 production in the lung. There was a significant positive correlation between IL-6 production in the lung and both PVR (r = 0.43; p = 0.001) and cGMP production in the lung (r = 0.498; p < 0.0001).


CONCLUSIONS
IL-6 production in the pulmonary circulation increases with the severity of CHF and is mainly associated with the activation of the sympathetic nervous system. The local production of IL-6 in the lung may modify PVR in patients with CHF.
Mabuchi
Naoko
N
First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Tsutamoto
Takayoshi
T
Wada
Atsuyuki
A
Ohnishi
Masato
M
Maeda
Keiko
K
Hayashi
Masaru
M
Kinoshita
Masahiko
M
D000328:Adult; D000368:Aged; D005260:Female; D006333:Heart Failure / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008168:Lung / Q000098:blood supply* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000276:immunology*
D015850:Interleukin-6; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine