Chest
Volume 121, Issue 4, April 2002, Pages 1195-1202
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Clinical Investigations
CARDIOLOGY
Relationship Between Interleukin-6 Production in the Lungs and Pulmonary Vascular Resistance in Patients With Congestive Heart Failure

https://doi.org/10.1378/chest.121.4.1195Get rights and content

Study objectives

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).

Patients and interventions

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-α, norepinephrine (NE), endothelin-1, atrial and brain natriuretic peptide, and cyclic guanosine monophosphate (cGMP) levels were determined.

Measurements and 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 β-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).

Conclusion

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.

Section snippets

Patients

Fifty patients with symptomatic left ventricular dysfunction (ie, left ventricular ejection fraction < 45%) who had undergone cardiac catheterization because of clinical indications were studied. We also selected nine age-matched control subjects, including two women, who had chest pain but normal coronary arteries. Written informed consent was obtained from all patients before their participation in the study, and the protocol was approved by the Human Investigations Committee of our

Hemodynamic Data

The left ventricular ejection fraction was significantly lower in patients with mild and severe CHF than in control subjects. In contrast, the mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure increased with the severity of CHF and were significantly higher in patients with severe CHF than in patients with mild CHF. PVR was also significantly higher in patients with severe CHF than in patients with mild CHF (Table 1).

Neurohumoral and Cytokine Data

Plasma levels of NE, ET-1,

Discussion

We showed here for the first time that there is plasma IL-6 production but not plasma TNF-α production in the pulmonary circulation of control subjects and patients with CHF, and that the IL-6 production increases with the severity of CHF and is related to the activation of the sympathetic nervous system. This is similar to our previously reported finding5 of IL-6 production in the peripheral vascular bed. At least a part of the increased plasma IL-6 levels in patients with CHF is secreted into

Conclusion

These results indicate that the IL-6 production in the pulmonary circulation increases with the severity of CHF and that the production of IL-6 is associated mainly with the activation of the sympathetic nervous system. The local production of IL-6 in the lung may modify PVR in patients with CHF.

ACKNOWLEDGMENT

We thank Ms. Ikuko Sakaguchi for excellent technical assistance. We also thank Mr. Daniel Mrozek for assistance in preparing the manuscript.

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    This study was supported by a Grant-in-Aid for Scientific Research, Japan.

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