Am. J. Respir. Crit. Care Med., Vol 152, No. 1, 07 1995, 329-335.
Pulmonary edema during IL-2 therapy: combined effect of increased permeability and hydrostatic pressure
Y Berthiaume, P Boiteau, G Fick, R Kloiber, GD Sinclair, C Fong, MC Poon and R Lafreniere
Department of Medicine, University of Calgary, Alberta, Canada.
Systemic administration of recombinant interleukin-2 (rIL-2) has been shown
to be promising against certain metastatic cancers. However, major side
effects, such as pulmonary edema, have limited its widespread use. Although
this pulmonary edema has been attributed to a vascular leak syndrome, this
hypothesis has not been verified in humans. The purpose of our study was to
determine both the severity and mechanism of pulmonary edema in seven
patients treated with rIL-2. The severity of edema was assessed by daily
evaluation of chest radiographs, using a semiquantitative scale, as well as
by repeated measurements of the alveolar-to-arterial oxygen gradient
(A-aDO2) in each patient. To determine the mechanism of pulmonary edema, we
serially measured in each patient the lung clearance of technetium 99m-
diethylenetriamine pentaacetic acid (DTPA) 99mTc-DTPA), the plasma levels
of Von Willebrand factor antigen, and the pulmonary capillary wedge
pressure (PCWP). Our results show that there was a gradual increase in the
chest radiography edema score that was paralleled by a significant increase
in A-aDO2 over its baseline value. During rIL-2 treatment, 99mTc-DTPA
clearance was augmented, and the plasma concentration of Von Willebrand
factor antigen was elevated. PCWP climbed from 7 to 14 mm Hg and serum
total protein fell from 66.1 to 42.1 gm/L. The results obtained indicate
that although pulmonary edema associated with rIL-2 treatment is partially
dependent on increased permeability of the lung, changes in hydrostatic and
oncotic forces may be the principal determinants of edema development.
