title: Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier.
abstract: Recombinant interleukin-2 (rIL-2) is an immunotherapeutic agent with efficacy against certain advanced cancers. The penetration of rIL-2 across the blood-cerebrospinal fluid (CSF) barrier was studied in 12 cancer patients who had no evidence of tumor involvement of the central nervous system. At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four). Bioassay showed the appearance of rIL-2 in lumbar CSF 4 to 6 hours after the first intravenous dose, a rise over 2 to 4 hours to a plateau of 3 to 9 U/ml, and clearance to less than 0.1 U/ml by 10 hours after the last dose. An abnormally elevated CSF albumin level in two of the twelve patients indicated alteration of the blood-brain barrier. There were no abnormalities in the CSF glucose level or white blood cell count. The CSF pharmacokinetics contrast with the rapid elimination of rIL-2 from plasma and demonstrate significant blood-CSF barrier penetration. These data support the possibility of achieving CSF levels of rIL-2 that are adequate to maintain activity of lymphokine-activated killer cells after parenteral administration, and argue for rIL-2-associated disruption of the human blood-brain barrier in some patients.
authors.affiliation: Clinical Neurosurgery Section, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland.
authors.forename: S C
authors.initials: SC
authors.lastname: Saris
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: R B
authors.initials: RB
authors.lastname: Friedman
authors.forename: J T
authors.initials: JT
authors.lastname: Rubin
authors.forename: D
authors.initials: D
authors.lastname: Barba
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000134:cerebrospinal fluid*; D004322:Drainage; D006801:Humans; D007376:Interleukin-2 / Q000097:blood / Q000134:cerebrospinal fluid*; D007700:Kinetics; D008161:Lumbosacral Region; D009949:Orientation / Q000187:drug effects; D009994:Osmolar Concentration; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins