Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep.
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)
Department of Medicine, Medical College of Virginia, Richmond.
F L
FL
Glauser
D E
DE
Bechard
G G
GG
DeBlois
A A
AA
Fowler
R E
RE
Merchant
G
G
Jesmok
R P
RP
Fairman
D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008196:Lymph / Q000166:cytology* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012756:Sheep
D001798:Blood Proteins; D007376:Interleukin-2; D011506:Proteins