Holmes, Alan, Soon, Elaine, Southwood, Mark, Machado, Rajiv, Barker, Lucy, Treacy, Carmen, Nicklin, Paul, Walker, Christoph, Budd, David, Pepke-Zaba, Joanna and Morrell, Nicholas (2010) ELEVATED LEVELS OF INFLAMMATORY CYTOKINES ARE STRONG PREDICTORS OF SURVIVAL IN IDIOPATHIC AND FAMILIAL PULMONARY ARTERIAL HYPERTENSION. Circulation, 122 (9). pp. 920-927.

Abstract

Background: Inflammation is known to be a feature of pulmonary arterial hypertension (PAH) and increased circulating levels of cytokines have been reported in patients with PAH. However, to date no information exists regarding 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 indices.

Methods and Results: We measured levels of serum cytokines (tumor necrosis factor-a interferon-γ and interleukins-1β, 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 (6MWD), and survival time from sampling to death or transplantation. Healthy volunteers served as controls (n=21). PAH patients had significantly higher levels of interleukins-1, 2, 6, 8, 10, 12p70 and TNFα compared to healthy controls. Kaplan-Meier analysis showed that levels of interleukins-6, 8, 10, and 12p70 had a profound impact on survival. For example, 5-year survival for patients with IL-6 levels of >9pg/ml was 29% compared with 63% for patients with levels ≤9pg/ml (p=0.008). In this PAH cohort, cytokine levels were superior to traditional markers of prognosis such as 6 minute walk distance and hemodynamics.

Conclusions: This study illustrates dysregulation of a broad range of inflammatory mediators in idiopathic and familial PAH, and demonstrates that cytokine levels have a profound impact on patient survival. They may prove useful biomarkers and provide insight into the contribution of inflammation in PAH.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Pulmonary hypertension; Inflammation; Interleukins
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez
Date Deposited:	13 Oct 2015 13:17
Last Modified:	13 Oct 2015 13:17
URI:	https://oak.novartis.com/id/eprint/1267