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Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep
F L Glauser1, D E Bechard, G G DeBlois
1Department of Medicine, Medical College of Virginia, Richmond.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|January 1, 1989
Summary
Recombinant interleukin 2 (rIL-2) therapy for advanced cancer causes "third space" syndrome. This study in sheep showed rIL-2 increases lung lymph flow and alters lymphocyte distribution, contributing to toxicity.
Area of Science:
- Immunology
- Oncology
- Pulmonary Medicine
Background:
- Recombinant interleukin 2 (rIL-2) is a novel cancer therapy.
- rIL-2 administration can lead to "third space" syndrome, characterized by pulmonary edema, respiratory distress, and hypoxemia.
- This toxicity limits rIL-2 treatment dosage and duration.
Purpose of the Study:
- To investigate the mechanisms of rIL-2-induced toxicity.
- To evaluate the effects of continuous rIL-2 infusion on hemodynamics, lung lymph dynamics, and cellular changes in a sheep model.
Main Methods:
- A sheep chronic lung lymph fistula model was utilized.
- Hemodynamics, arterial blood gases, lung lymph flow (QL), and blood/lymph cellular composition were measured.
- Continuous rIL-2 infusion (9 x 10(5) U/kg) was administered for 3 days.
Main Results:
- Moderate systemic hypotension and mild pulmonary hypertension were observed.
- Alveolar-arterial PO2 gradient increased, and QL significantly elevated.
- Leukocyte counts increased, with significant alterations in blood and lung lymph lymphocyte percentages and size.
Conclusions:
- rIL-2 administration induces significant hemodynamic and pulmonary changes.
- Altered lung lymph dynamics and lymphocyte shifts contribute to rIL-2 toxicity.
- Further research is needed to mitigate these adverse effects.