[Pharmacokinetics and toxicity of intrathecal administration of recombinant interleukin 2].

In order to contribute to the development of adoptive immunotherapy against malignant brain tumors, the pharmacokinetics and toxicity of intrathecally administered recombinant interleukin-2 in dogs and human patients were analyzed. The pharmacokinetics showed that a high concentration of IL-2 was maintained in the intrathecal cavity in both dogs and human (t1/2 = 1.41 and 1.68 hours, respectively) after administration. However, no activity of IL-2 was detected in the cerebrospinal fluid after the systemic administration of rIL-2 in one dog. No meningitis, ventriculitis or degeneration of neurons was seen histopathologically in dogs 3 weeks after the intrathecal administration of rIL-2 (200 units). A high concentration of IL-2 in the tumor cavity was maintained for a very long time (t1/2 = 14.8 hours) after the intratumoral administration of rIL-2 in one of the patients. Although low-grade fever and mild headache were sometimes observed after the intrathecal administration of rIL-2 in patients, there was no other side effect mentioned. Intrathecal or intratumoral administration of rIL-2 appeared to be an valuable procedure which should be evaluated in conjunction with adoptive immunotherapy against malignant brain tumors.