Chest
Clinical InvestigationsCARDIOLOGYRelationship Between Interleukin-6 Production in the Lungs and Pulmonary Vascular Resistance in Patients With Congestive Heart Failure
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.
References (37)
- et al.
Proinflammatory cytokine levels in patients with depressed left ventricular ejection: a report from the studies of left ventricular dysfunction (SOLVD)
J Am Coll Cardiol
(1996) - et al.
Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy
Am J Cardiol
(1996) - et al.
Role of cytokines in the mechanism of action of Amlodipine: the PRAISE heart failure trial
J Am Coll Cardiol
(1997) - et al.
Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognosis predictor in patients with congestive heart failure
J Am Coll Cardiol
(1998) - et al.
Prognostic value of serum cytokines in patients with congestive heart failure
J Heart Lung Transplant
(2000) - et al.
High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure
J Am Coll Cardiol
(2000) The biology of interleukin-6
Blood
(1989)- et al.
Induction of interleukin 6 (IL-6) by hypoxia in vascular cells: central role of the binding site for nuclear factor-IL-6
J Biol Chem
(1995) - et al.
Synthesis of interleukin-6 (interferon-β 2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP
J Biol Chem
(1988) - et al.
Cytokine networks in the regulation of inflammation and fibrosis in the lung
Chest
(1990)
Relation between endothelin-1 spillover in the lungs and pulmonary vascular resistance in patients with chronic heart failure
J Am Coll Cardiol
Uncoupling of atrial natriuretic peptide extraction and cyclic guanosine monophosphate production in the pulmonary circulation in patients with severe heart failure
J Am Coll Cardiol
Catecholamines and lipopolysaccharide synergistically induce the release of interleukin-6 from thymic epithelial cells
J Neuroimmunol
Elevated circulating levels of tumor necrosis factor in severe chronic heart failure
N Engl J Med
Continuous activation of gp 130, a signal-transducing receptor component for interleukin-6-related cytokines, causes myocardial hypertrophy in mice
Proc Natl Acad Sci U S A
Negative inotropic effects of cytokines on the heart mediated by nitric oxide
Science
Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 production secretion by human endothelial cells
J Immunol
Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6
J Clin Invest
Cited by (24)
The role of interleukin-6 in UVA protection against UVB-induced immunosuppression
2009, Journal of Investigative DermatologyCitation Excerpt :The tissue level of cGMP is determined by the balance of its synthesis by guanylyl cyclase and its normal degradation by the cellular phosphodiesterases. Therefore, either guanylyl cyclase activity is IL-6 dependent, consistent with the immunological inactivity of the CO-RM in IL-6 deficiency, and with reports indicating a positive correlation between IL-6 and cGMP levels in neural or lung tissue (Ma and Zhu, 1996; Mabuchi et al., 2002), or phosphodiesterase activity is normally inhibited by IL-6. Future studies should shed light on possible cytokine regulation of these enzyme activities.
Effects of interleukin-6 produced in coronary circulation on production of C-reactive protein and coronary microvascular resistance
2005, American Journal of CardiologyUsefulness of C-reactive protein as an independent predictor of death in patients with ischemic cardiomyopathy
2005, American Journal of CardiologyCytokine response to pulmonary thromboendarterectomy
2004, ChestCitation Excerpt :Because the avoidance of positive inotropic catecholamines appears to be important,35 the maintenance of adequate systemic BP requires careful titration with vasopressors such as norepinephrine. Since PTE is a major insult to the pulmonary vascular endothelium, which is known to be a source of IL-6 release,20 we hypothesized that IL-6 expression may be responsible for the systemic vasoplegia in CTEPH patients after undergoing PTE. In fact, statistical analysis revealed a positive correlation between postoperative peak IL-6 levels and the severity of CTEPH (compared to preoperative MPAP and PVR levels).
Peri-Operative Changes of Inflammatory Markers and Their Implications in Pulmonary Endarterectomy
2022, Reviews in Cardiovascular Medicine
This study was supported by a Grant-in-Aid for Scientific Research, Japan.