Permeability of the mouse blood–brain barrier to murine interleukin-2: predominance of a saturable efflux system

2004 ◽  
Vol 18 (5) ◽  
pp. 434-442 ◽  
Author(s):  
William A. Banks ◽  
Michael L. Niehoff ◽  
Steven S. Zalcman
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Maarja Andaloussi Mäe ◽  
Tian Li ◽  
Giacomo Bertuzzi ◽  
Elisabeth Raschperger ◽  
Michael Vanlandewijck ◽  
...  

2004 ◽  
Vol 64 (9) ◽  
pp. 3296-3301 ◽  
Author(s):  
Salvatore Cisternino ◽  
Claire Mercier ◽  
Fanchon Bourasset ◽  
Françoise Roux ◽  
Jean-Michel Scherrmann

1988 ◽  
Vol 69 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Stephen C. Saris ◽  
Steven A. Rosenberg ◽  
Robert B. Friedman ◽  
Joshua T. Rubin ◽  
David Barba ◽  
...  

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 At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four).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


1989 ◽  
Vol 70 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Joseph T. Alexander ◽  
Stephen C. Saris ◽  
Edward H. Oldfield

✓ Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 ± 14.6 and 35.8 ± 6.0, respectively, mean ± standard error of the mean) were larger (p < 0.05) than in control animals (61.4 ± 6.4 and 14.6 ± 2.2, respectively). In contrast, in normal frontal and occipital tissue contralateral to the tumor-bearing hemisphere, there was no significant difference between the transfer constants in IL-2-treated and control animals. Furthermore, treatment of animals with IL-2 excipient caused no change in permeability as compared to animals treated with Hanks' balanced salt solution. Parenteral injection of IL-2 increases blood-brain barrier disruption in tumor-bearing rat brain but does not increase the vascular permeability of normal brain. Methods to prevent this increased tumor vessel permeability are required before parenteral IL-2 can be used safely for the treatment of primary or metastatic brain tumors.


1978 ◽  
Vol 235 (4) ◽  
pp. F331-F337 ◽  
Author(s):  
H. F. Cserr ◽  
B. J. Berman

Mechanisms and pathways of 125I and 35SCN efflux from the brain were investigated in anesthetized rats. Tracers were injected into the caudate nucleus through a guide cannula implanted 1 wk previously and concentrations of isotope in brain and cerebrospinal fluid (CSF) were determined at various times after injection. 125I clearance from the brain followed a single exponential curve. In control rats 36.2% of the 125I remained in the brain 30 min after injection and 60.4% in rats pretreated with perchlorate. Comparable values for 35SCN were 25.8% in control rats, 41.0% with perchlorate, and 39.7% with iodide loading. Estimates of 125I and 35SCN effluxes from the brain via the blood-brain barrier and CSF pathways suggest that greater than 95% of efflux crosses the blood-brain barrier. These results indicate that 1)iodide and thiocyanate are transported across the blood-brain barrier by a common mechanism, and 2) this efflux system is an important factor in the control of the distributions of iodide and thiocyanate in the central nervous system.


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