Interleukin-6 and Tumor Necrosis Factor-α Are Associated with Quality of Life–Related Symptoms in Pulmonary Arterial Hypertension

Matura, Lea Ann; Ventetuolo, Corey E.; Palevsky, Harold I.; Lederer, David J.; Horn, Evelyn M.; Mathai, Stephen C.; Pinder, Diane; Archer-Chicko, Christine; Bagiella, Emilia; Roberts, Kari E.; Tracy, Russell P.; Hassoun, Paul M.; Girgis, Reda E.; Kawut, Steven M.

doi:10.1513/annalsats.201410-463oc

Cited by 34 publications

(24 citation statements)

References 52 publications

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“…42 However, higher IL-6 levels in this population were linked to increased fatigue, anxiety and depression. 43 Our pilot data provide preliminary evidence that slow-paced respiration may decrease IL-6 levels leading to improved depressive symptoms and fatigue. Sleep loss can result in increased proinflammatory cytokines (IL-6) and poor sleep quality.…”

Section: Discussionmentioning

confidence: 66%

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

et al. 2017

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Objective To determine the feasibility of using slow-paced respiration therapy to treat symptoms in women with pulmonary arterial hypertension (PAH). Background People with PAH report increased dyspnea, fatigue and sleep disturbance that can impair health-related quality of life (HRQOL). Methods Ten women with PAH received 8-weeks of daily, 15 minute sessions using slow-paced respiration therapy via the RESPeRATE™ device. Participants had baseline and follow up assessments including plasma norepinephrine and interleukin-6 (IL-6), self-report questionnaires to measure dyspnea, fatigue, depressive symptoms, sleep and HRQOL along with 7-day actigraphy and sleep diaries. Results The mean age was 50 years. Adherence to the intervention was 92%. There was decrease in median IL-6 levels [1.3 ± 0.5 to 1.1 ± 0.4, 95% CI (0.03–0.43)] over the study period. Sleep disturbance decreased, depressive symptoms decreased and HRQOL scores decreased (higher scores indicate worse HRQOL). Conclusions In this pilot study, slow-paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL-6.

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Section: Discussionmentioning

confidence: 66%

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

et al. 2017

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“…In animal models, PH development has been seen after the administration of recombinant IL-6 and also in IL-6 transgenic mice [103][104][105], whereas IL-6 knockout mice have shown resistance to hypoxia-induced PH development [106]. In clinical studies, IL-6 has shown to correlate to survival and quality of life in IPAH patients [80,107] and in predicting long-term responses to PEA in CTEPH patients [98]. In a recent study, cytokine clusters were made in PAH patients using machine learning.…”

Section: Inflammatory Diagnostic and Prognostic Biomarkers In Pah Andmentioning

confidence: 99%

Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: An Immunological Perspective

Koudstaal

Boomars

Kool

2020

JCM

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Pulmonary hypertension (PH) is a debilitating progressive disease characterized by increased pulmonary arterial pressures, leading to right ventricular (RV) failure, heart failure and, eventually, death. Based on the underlying conditions, PH patients can be subdivided into the following five groups: (1) pulmonary arterial hypertension (PAH), (2) PH due to left heart disease, (3) PH due to lung disease, (4) chronic thromboembolic PH (CTEPH), and (5) PH with unclear and/or multifactorial mechanisms. Currently, even with PAH-specific drug treatment, prognosis for PAH and CTEPH patients remains poor, with mean five-year survival rates of 57%–59% and 53%–69% for PAH and inoperable CTEPH, respectively. Therefore, more insight into the pathogenesis of PAH and CTEPH is highly needed, so that new therapeutic strategies can be developed. Recent studies have shown increased presence and activation of innate and adaptive immune cells in both PAH and CTEPH patients. Moreover, extensive biomarker research revealed that many inflammatory and immune markers correlate with the hemodynamics and/or prognosis of PAH and CTEPH patients. Increased evidence of the pathological role of immune cells in innate and adaptive immunity has led to many promising pre-clinical interventional studies which, in turn, are leading to innovative clinical trials which are currently being performed. A combination of immunomodulatory therapies might be required besides current treatment based on vasodilatation alone, to establish an effective treatment and prevention of progression for this disease. In this review, we describe the recent progress on our understanding of the involvement of the individual cell types of the immune system in PH. We summarize the accumulating body of evidence for inflammation and immunity in the pathogenesis of PH, as well as the use of inflammatory biomarkers and immunomodulatory therapy in PAH and CTEPH.

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“…Since substantially elevated circulating levels of certain inflammatory mediators, including IL-6, have been found to correlate with worse clinical outcomes, quality of life-related symptoms, and/or death in PAH patients (3)(4)(5), the sustained inflammation in PAH has moved from a common histopathological finding to a potential contributor to the perpetuation of the disease. However, the field is currently lacking a mechanistic vantage point to understand how inflammation, and in particular IL-6-dependent signaling, contributes to the disease pathogenesis, a prerequisite for the development of novel therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, IL-6-overexpressing mice spontaneously develop PH and pulmonary vascular remodeling, whereas Il6-knockout mice are more resistant to the development of PH induced by chronic hypoxia (11,12). In this context, although blockade of IL-6 signaling represents a promising target (3,4,(9)(10)(11)(12)(13)(14), it remains unclear how this signaling pathway determines the progression and ultimately the severity of the disease, and it is therefore difficult to develop therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

Tamura¹,

Phan²,

Tu³

et al. 2018

Journal of Clinical Investigation

132

115

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Pulmonary arterial hypertension (PAH) is characterized by a progressive accumulation of pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterioles leading to the narrowing of the lumen, right heart failure, and death. Although most studies have supported the notion of a role for IL-6/glycoprotein 130 (gp130) signaling in PAH, it remains unclear how this signaling pathway determines the progression of the disease. Here, we identify ectopic upregulation of membrane-bound IL-6 receptor (IL6R) on PA-SMCs in PAH patients and in rodent models of pulmonary hypertension (PH) and demonstrate its key role for PA-SMC accumulation in vitro and in vivo. Using Sm22a-Cre Il6rfl/fl, which lack Il6r in SM22A-expressing cells, we found that these animals are protected against chronic hypoxia-induced PH with reduced PA-SMC accumulation, revealing the potent pro-survival potential of membrane-bound IL6R. Moreover, we determine that treatment with IL6R-specific antagonist reverses experimental PH in two rat models. This therapeutic strategy holds promise for future clinical studies in PAH.

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Interleukin-6 and Tumor Necrosis Factor-α Are Associated with Quality of Life–Related Symptoms in Pulmonary Arterial Hypertension

Abstract: IL-6 and tumor necrosis factor-α levels are associated with certain quality of life domains in patients with pulmonary arterial hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).

Cited by 34 publications

References 52 publications

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: An Immunological Perspective

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

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