Blood-brain barrier dysfunction in cats following recombinant interleukin-2 infusion

• Published in: Cancer research (Chicago, Ill.) Ill.), 1987-11, Vol.47 (21), p.5765-5770
• Main Authors: ELLISON, M. D, POVLISHOCK, J. T, MERCHANT, R. E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Brain - blood supply; Brain - ultrastructure; Cats; Drug toxicity and drugs side effects treatment; Horseradish Peroxidase - metabolism; Immunoglobulin G - metabolism; Interleukin-2 - toxicity; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Permeability; Pharmacology. Drug treatments; Recombinant Proteins - toxicity; Sodium Dodecyl Sulfate - toxicity
• ISSN: 0008-5472; 1538-7445

The effects of systemic human recombinant interleukin-2 (rIL-2) infusion upon blood-brain barrier status and cerebral vascular ultrastructure were examined in cats. Each of eight animals received a single bolus i.v. infusion of rIL-2 (100,000 units/kg). Six control animals were infused with rIL-2 excipient only. Following a 1-h postinfusion survival time, the brain tissue of five rIL-2 infused and three excipient infused animals was processed and examined by light microscopy and electron microscopy for evidence of altered cerebrovascular permeability to systemically circulating horseradish peroxidase. The brain tissue of three additional rIL-2 infused animals and three excipient infused animals, sacrificed 4 h postinfusion, was examined at the light microscopic and electron microscopic levels for the presence of extravasated endogenous IgG. All animals infused with rIL-2 and four of six excipient infused animals showed increased cerebrovascular permeability to the probe used. Altered blood-brain barrier permeability, when present, was recognized in multiple loci throughout the brain, being most prominent within white matter regions. Horseradish peroxidase and IgG were observed within perivascular basal laminae and within the interstices of the brain parenchyma. Numerous endothelial lesions were observed as was flooding of endothelial cytoplasm by horseradish peroxidase or IgG. Every animal studied, regardless of permeability status, showed, within the perivascular brain parenchyma, numerous disrupted neuronal and glial processes as well as expanded intercellular spaces. This study suggests that a single systemic infusion of rIL-2 profoundly alters blood-brain barrier integrity and cerebrovascular morphological integrity. The data also suggest that some of the observed cerebrovascular effects of systemic rIL-2 infusion are due to components of the vehicle for rIL-2.