Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier.
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 At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four).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.
Saris
S C
SC
Clinical Neurosurgery Section, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland.
Rosenberg
S A
SA
Friedman
R B
RB
Rubin
J T
JT
Barba
D
D
Oldfield
E H
EH
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
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins