Journal of Applied Physiology, Vol 66, Issue 1 128-134, Copyright © 1989 by American Physiological Society
Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep
F. L. Glauser, D. E. Bechard, G. G. DeBlois, A. A. Fowler, R. E. Merchant, G. Jesmok and R. P. Fairman
Department of Medicine, Medical College of Virginia, Richmond.
Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for
patients with far-advanced cancer, is associated with a "third space"
syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which
limits the dose and duration of treatment. To extend our knowledge
regarding this toxicity, we established a sheep chronic lung lymph fistula
model and measured hemodynamics, arterial blood gases, caudal mediastinal
(lung) lymph flow (QL), and blood and lung lymph cellular changes before,
during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5)
U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an
increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2
infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3
+/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change
in lymph-to-plasma protein ratio. The leukocyte count increased
significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The
percentage of blood lymphocytes decreased significantly by day 1 of rIL-2
infusion, returned to base-line levels on day 3, and significantly
increased on day 2 of recovery. Lung lymph lymphocytes decreased
significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their
size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P
less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung
lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250
WORDS)
