Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer

Abstract

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.

Immunoenzymetric Assay of Mouse and Human Cytokines Using NIP‐Labeled Anti‐Cytokine Antibodies

“…By using an enzyme-conjugated antibody specific for the NIP hapten, rather than enzyme-conjugated avidin or streptavidin to detect biotin, potential sources of nonspecificity-e.g., endogenous sample biotin or soluble adhesion molecules bearing RGD or RYD recognition sequences-can be avoided. The method described in this unit has allowed successful measurement of different cytokines in a wide variety of clinical samples including conditioned medium (Hirayama et al, 1994;Sander et al, 1993), serum and plasma (Butterfield et al, 1992;Limaye et al, 1991;van Haelst Pisani et al, 1991), ascites (Gotlieb et al, 1992), amniotic fluid (Heyborne et al, 1994), and bronchoalveolar lavage fluid (Sedgwick et al, 1991).…”