Administration of interleukin-2 (IL-2) results in increased plasma
concentrations of IL-5 and eosinophilia in patients with cancer
C van Haelst Pisani, JS Kovach, H Kita, KM Leiferman, GJ Gleich, JE Silver, R Dennin and JS Abrams
Department of Oncology, Mayo Clinic, Rochester, MN 55905.
Peripheral eosinophilia is almost invariably observed during the course of
interleukin-2 (IL-2) therapy and is frequently accompanied by the
development of a capillary leak syndrome characterized by edema, weight
gain, and oliguria. We studied five patients with advanced malignancy
treated with IL-2. Eosinophilia was not present initially but developed in
all patients late in the course of therapy, with counts ranging from
2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship
between the infusion of IL-2 and the appearance of elevated plasma
concentrations of IL-5, a growth factor for eosinophils.
Granulocyte-macrophage colony-stimulating factor was not detectable in
plasma. IL-4 and gamma-interferon plasma levels were variably elevated.
Plasma concentrations of major basic protein, a toxic eosinophil granule
protein, began increasing before eosinophil counts increased. By the time
of the third IL-2 infusion, high concentrations of major basic protein were
present in all five patients (up to 5,600 ng/mL) and skin biopsies showed
major basic protein deposition in the dermis. Four patients developed
significant capillary leak syndrome and all of these patients showed
markedly elevated major basic protein levels. The lowest peak plasma
concentration of major basic protein (1,751 ng/mL) was observed in the one
patient who did not develop edema and weight gain. These results suggest
that IL-2 induces IL-5 leading to marked peripheral eosinophilia and
extravascular eosinophil degranulation. The release of toxic eosinophil
products at extravascular sites and in the circulation may contribute to
the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.
Volume 78,
Issue 6,
pp. 1538-1544,
09/15/1991
Copyright © 1991 by The American Society of Hematology
