PULMONARY-EDEMA DURING IL-2 THERAPY - COMBINED EFFECT OF INCREASED PERMEABILITY AND HYDROSTATIC-PRESSURE

Systemic administration of recombinant interleukin-2 (rlL-2) has been shown to be promising against certain metastatic cancers. However, maj or side effects, such as pulmonary edema, have limited its widespread use. Although this pulmonary edema has been attributed to a vascular l eak syndrome, this hypothesis has not been verified in humans. The pur pose of our study was to determine both the severity and mechanism of pulmonary edema in seven patients treated with rlL-2. The severity of edema was assessed by daily evaluation of chest radiographs, using a s emiquantitative scale, as well as by repeated measurements of the alve olar-to-arterial oxygen gradient (A-aDo(2)) in each patient. To determ ine the mechanism of pulmonary edema, we serially measured in each pat ient the lung clearance of technetium 99m-diethylenetriamine pentaacet ic acid (DTPA) (TC)-T-99m-DTPA), the plasma levels of Von Willebrand f actor antigen, and the pulmonary capillary wedge pressure (PCWP). Our results show that there was a gradual increase in the chest radiograph y edema score that was paralleled by a significant increase in A-aDo(2 ) over its baseline value. During rlL-2 treatment, (TC)-T-99m-DTPA cle arance was augmented, and the plasma concentration of Von Willebrand f actor 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 indica te that although pulmonary edema associated with rlL-2 treatment is pa rtially dependent on increased permeability of the lung, changes in hy drostatic and oncotic forces may be the principal determinants of edem a development.