Clearance rates and systemic effects of intravenously administered interleukin 2 (IL-2) containing preparations in human subjects

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Abstract
The present study was designed to examine the feasibility of in vivo administration of interleukin 2 (IL-2) to induce cytotoxic cell activity against tumours in human subjects. IL-2 was prepared from blood leukocytes stimulated with phytohaemagglutinin (PHA) and partially purified by membrane chromatography to exclude PHA. Administration of different amounts of IL-2 in vivo to 2 patients with melanoma revealed that the initial level of IL-2 in the circulation was related to the dose given and had a half-life of approximately 22.5 minutes. The initial and subsequent levels of IL-2 were lower than that expected to occur from equilibration in plasma and extracellular fluid. This was not apparently due to inactivation by serum factors because fresh human serum had little effect in vitro on the induction of mitogenic or cytotoxic activity by IL-2. Spontaneous division of lymphocytes was increased following IL-2 administration and it is suggested that clearance of IL-2 in vivo may reflect, in part, absorption by activated lymphocytes in the circulation. Side effects noted shortly after administration of the partially-purified IL-2 preparations included transient pyrexia, hypoglycaemia, increased cortisol levels, lymphocytopenia and signs of mild intravascular coagulation. No long-term effects were noted. These initial results suggest that systemic injection of purified preparations of II-2 may be a feasible approach to induce cytotoxic T cells in vivo.