SESSION TITLE: Cytokines/Cellular Interactions Posters
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM
PURPOSE: Metastatic renal cell carcinomas and melanomas impart poor prognoses. High Dose Interleukin-2 (HD IL-2) therapy may improve prognosis but clinical utility and efficacy is limited by systemic inflammation and acute organ failure including acute respiratory failure from pulmonary edema. In tissue models, IL-2 stimulates Angiopoietin-2 secretion, which increases endothelial permeability and causes pulmonary edema. However, this relationship has not been fully elucidated in human subjects. Further, the relevance of plasma angiopoietin-2 to organ function is not clear. We hypothesized that plasma Angiopoietin-2 concentrations increase during HD IL-2 therapy, and are relevant to clinical physiology.
METHODS: We enrolled 13 subjects admitted to receive HD IL2. On each treatment day, blood samples and pulmonary function testing were obtained. The plasma concentrations of Angiopoietin-2 and Interleukin-6 were measured with ELISA.
RESULTS: At baseline, the mean Angiopoietin-2 concentration was 2.5 ng/mL (SD 1.0 ng/mL). Angiopoietin-2 concentrations increased during treatment: the mean concentration on the penultimate day was 16.0 ng/mL (SD 4.5 ng/mL) and 18.6 ng/mL (SD 4.9 ng/mL; p < 0.05 vs penultimate) during the last day of therapy. The Forced Expiratory Volume in one second (FEV-1) decreased during treatment. Interestingly, we found that FEV-1 correlated negatively with plasma Angiopoietin-2 concentrations (Spearman r=-0.78, p < 0.0001). Plasma Angiopoietin-2 concentrations also correlated with plasma Interleukin-6 concentration (r = 0.61, p < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (r = 0.68, p < 0.0001).
CONCLUSIONS: Plasma Angiopoietin-2 concentration increases during HD IL-2 administration, and correlates with pulmonary function.
CLINICAL IMPLICATIONS: HD IL-2 may serve as a clinical model of sepsis and acute lung injury. Further investigation is warranted.
DISCLOSURE: The following authors have nothing to disclose: Katie Gores, Angela Delsing, Sara Kraus, Shinkai Hakimi, Linda Powers, Daniel Vaena, Mohammed Milhem, Martha Monick, Kevin Doerschug
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