Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier

S. C. Saris, S. A. Rosenberg, R. B. Friedman, J. T. Rubin, D. Barba, E. H. Oldfield

Research output: Contribution to journalArticlepeer-review

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 At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four).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.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalJournal of neurosurgery
Volume69
Issue number1
DOIs
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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