Plasma angiopoietin-2 concentrations are related to impaired lung function, and organ failure in a clinical cohort receiving high dose interleukin-2 therapy

Kathryn M Gores; Angela S Delsing; Sara J Kraus; Linda Powers; Daniel A Vaena; Mohammed M Milhem; Martha Monick; Kevin C Doerschug

doi:10.1097/SHK.0000000000000188

Back

Plasma angiopoietin-2 concentrations are related to impaired lung function, and organ failure in a clinical cohort receiving high dose interleukin-2 therapy

Journal article

Open access

Plasma angiopoietin-2 concentrations are related to impaired lung function, and organ failure in a clinical cohort receiving high dose interleukin-2 therapy

Kathryn M Gores, Angela S Delsing, Sara J Kraus, Linda Powers, Daniel A Vaena, Mohammed M Milhem, Martha Monick and Kevin C Doerschug

Shock (Augusta, Ga.), Vol.42(2), pp.115-120

08/2014

DOI: 10.1097/SHK.0000000000000188

PMCID: PMC4467554

PMID: 24727870

Files and links (1)

url

https://doi.org/10.1097/SHK.0000000000000188View

Published (Version of record) Open Access

Abstract

Introduction: The pathophysiology and therapeutic options in sepsis-induced lung injury remain elusive. High-dose interleukin 2 therapy (HDIL-2) is an important protocol for advanced malignancies but is limited by systemic inflammation and pulmonary edema that is indistinguishable from sepsis. In preclinical models, IL-2 stimulates angiopoietin 2 (AngP-2) secretion, which increases endothelial permeability and causes pulmonary edema. However, these relationships have not been fully elucidated in humans. Furthermore, the relevance of plasma AngP-2 to organ function is not clear. We hypothesized that plasma AngP-2 concentrations increase during HDIL-2 and are relevant to clinical pathophysiology. Methods: We enrolled 13 subjects with metastatic melanoma or renal cell carcinoma admitted to receive HDIL-2 and collected blood and spirometry data daily. The plasma concentrations of AngP-2 and IL-6 were measured with enzyme-linked immunosorbent assay. Results: At baseline, the mean AngP-2 concentration was 2.5 (SD, 1.0) ng/mL. Angiopoietin 2 concentrations increased during treatment: the mean concentration on the penultimate day was 16.0 (SD, 4.5) ng/mL and increased further to 18.6 (SD, 4.9) ng/mL (P < 0.05 vs. penultimate) during the last day of therapy. The forced expiratory volume in 1 s decreased during treatment. Interestingly, plasma AngP-2 concentrations correlated negatively with forced expiratory volume in 1 s (Spearman r = -0.78, P < 0.0001). Plasma AngP-2 concentrations also correlated with plasma IL-6 concentrations (r = 0.61, P < 0.0001) and Sequential Organ Failure Assessment scores (r = 0.68, P < 0.0001). Conclusions: Plasma AngP-2 concentrations increase during HDIL-2 administration and correlate with pulmonary dysfunction. High-dose IL-2 may serve as a clinical model of sepsis and acute lung injury. Further investigation is warranted.

Interleukin-2

Systemic Inflammatory Response Syndrome

Acute Respiratory Distress Syndrome

Acute Lung Injury

Details

Title: Subtitle: Plasma angiopoietin-2 concentrations are related to impaired lung function, and organ failure in a clinical cohort receiving high dose interleukin-2 therapy
Creators: Kathryn M Gores - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Angela S Delsing - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Sara J Kraus - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Linda Powers - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Daniel A Vaena - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Mohammed M Milhem - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Martha Monick - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Kevin C Doerschug - Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive Iowa City, IA 52242, United States of America
Resource Type: Journal article
Publication Details: Shock (Augusta, Ga.), Vol.42(2), pp.115-120
DOI: 10.1097/SHK.0000000000000188
PMID: 24727870
PMCID: PMC4467554
NLM abbreviation: Shock
ISSN: 1073-2322
eISSN: 1540-0514
Language: English
Date published: 08/2014
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; Nursing; Internal Medicine
Record Identifier: 9984094381102771

Metrics

21 Record Views

7 Times Cited - Web of Science