title: Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation.
abstract: Expression of the low-affinity interleukin-2 (IL-2) receptor molecule (TAC) has been associated with lymphocyte activation, in vitro and in vivo [Greene WC (1987) Clin Res 35:439]. We have used an enzyme-linked immunosorbent assay (ELISA) to quantify the role of released and cell-bound IL-2 receptor following in vitro or in vivo activation of human lymphocytes with IL-2. In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells. In 12 patients receiving high-dose IL-2 for the treatment of various malignant neoplasms, the levels of IL-2 receptor released into the serum rose dramatically during the IL-2 infusion, and then fell following cessation of the IL-2 infusion. This heightened release of IL-2 receptor into the serum occurred during the episodes of profound lymphopenia that developed within hours after patients began an IL-2 infusion. Following each 4-day infusion of IL-2, a rebound lymphocytosis was observed, as has been previously reported. Serum IL-2 receptor levels do not rebound in parallel; rather, they reach a plateau near the end of the 4-day infusion and then decrease upon cessation of IL-2. These changes in serum IL-2 receptor levels accompany changes in lytic activity of circulating PBL on Daudi target cells. These results suggest that lymphocyte populations exposed to IL-2 in vivo are activated to become cytotoxic, release TAC, and relocate in non-peripheral blood compartments. Following cessation of the IL-2 infusion these activated lymphocytes return to the peripheral circulation and do not secrete TAC as vigorously as while influenced directly by the IL-2 infusion.
authors: Department of Human Oncology, University of Wisconsin Medical School, Madison.
authors: S D
authors: SD
authors: Voss
authors: J A
authors: JA
authors: Hank
authors: C A
authors: CA
authors: Nobis
authors: P
authors: P
authors: Fisch
authors: J A
authors: JA
authors: Sosman
authors: P M
authors: PM
authors: Sondel
mesh_terms: D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000627:therapeutic use*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008545:Melanoma / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000097:blood* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2