Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension

Elaine Soon; Alan M. Holmes; Carmen M. Treacy; Natalie J. Doughty; Laura Southgate; Rajiv D. Machado; Richard C. Trembath; Simon Jennings; Lucy Barker; Paul Nicklin; Christoph Walker; David C. Budd; Joanna Pepke-Zaba; Nicholas W. Morrell

doi:10.1161/CIRCULATIONAHA.109.933762

Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension

Elaine Soon, Alan M. Holmes, Carmen M. Treacy, Natalie J. Doughty, Laura Southgate, Rajiv D. Machado, Richard C. Trembath, Simon Jennings, Lucy Barker, Paul Nicklin, Christoph Walker, David C. Budd, Joanna Pepke-Zaba, Nicholas W. Morrell

Medical & Molecular Genetics

Research output: Contribution to journal › Article › peer-review

652 Citations (Scopus)

Abstract

Background-Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. Methods and Results-We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1 beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1 beta, -2, - 4, - 6, - 8, - 10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels

Original language	English
Pages (from-to)	921 - U90
Number of pages	8
Journal	Circulation (Baltimore)
Volume	122
Issue number	9
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.109.933762
Publication status	Published - 31 Aug 2010

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10.1161/CIRCULATIONAHA.109.933762

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Soon, E., Holmes, A. M., Treacy, C. M., Doughty, N. J., Southgate, L., Machado, R. D., Trembath, R. C., Jennings, S., Barker, L., Nicklin, P., Walker, C., Budd, D. C., Pepke-Zaba, J., & Morrell, N. W. (2010). Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension. Circulation (Baltimore), 122(9), 921 - U90. https://doi.org/10.1161/CIRCULATIONAHA.109.933762

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title = "Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension",

abstract = "Background-Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. Methods and Results-We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1 beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1 beta, -2, - 4, - 6, - 8, - 10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels ",

author = "Elaine Soon and Holmes, {Alan M.} and Treacy, {Carmen M.} and Doughty, {Natalie J.} and Laura Southgate and Machado, {Rajiv D.} and Trembath, {Richard C.} and Simon Jennings and Lucy Barker and Paul Nicklin and Christoph Walker and Budd, {David C.} and Joanna Pepke-Zaba and Morrell, {Nicholas W.}",

year = "2010",

month = aug,

day = "31",

doi = "10.1161/CIRCULATIONAHA.109.933762",

language = "English",

volume = "122",

pages = "921 -- U90",

journal = "Circulation (Baltimore)",

issn = "1524-4539",

publisher = "American Heart Association, Inc.",

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Soon, E, Holmes, AM, Treacy, CM, Doughty, NJ, Southgate, L , Machado, RD , Trembath, RC, Jennings, S, Barker, L, Nicklin, P, Walker, C, Budd, DC, Pepke-Zaba, J & Morrell, NW 2010, 'Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension', Circulation (Baltimore), vol. 122, no. 9, pp. 921 - U90. https://doi.org/10.1161/CIRCULATIONAHA.109.933762

TY - JOUR

T1 - Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension

AU - Soon, Elaine

AU - Holmes, Alan M.

AU - Treacy, Carmen M.

AU - Doughty, Natalie J.

AU - Southgate, Laura

AU - Machado, Rajiv D.

AU - Trembath, Richard C.

AU - Jennings, Simon

AU - Barker, Lucy

AU - Nicklin, Paul

AU - Walker, Christoph

AU - Budd, David C.

AU - Pepke-Zaba, Joanna

AU - Morrell, Nicholas W.

PY - 2010/8/31

Y1 - 2010/8/31

N2 - Background-Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. Methods and Results-We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1 beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1 beta, -2, - 4, - 6, - 8, - 10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels

AB - Background-Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. Methods and Results-We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1 beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1 beta, -2, - 4, - 6, - 8, - 10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels

U2 - 10.1161/CIRCULATIONAHA.109.933762

DO - 10.1161/CIRCULATIONAHA.109.933762

M3 - Article

SN - 1524-4539

VL - 122

SP - 921 - U90

JO - Circulation (Baltimore)

JF - Circulation (Baltimore)

IS - 9

ER -

Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension

Abstract

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