Evaluation in mice of the capillary leak syndrome (CLS) mediated by the systemic administration of recombinant interleukin-2 (IL-2)
Since a CLS with interstitial pulmonary edema has been the major toxicity of IL-2 administration in humans, the authors studied this CLS in mice by quantitating the IL-2 mediated, tissue extravasation (Ex) of intravenously injected /sup 125/I-bovine serum albumin (BSA). Mice received saline (HBSS) or 200,000 U of IL-2 intraperitoneally thrice daily from day 0-6 before tissues were counted. A permeability index (PI) was calculated by dividing the mean counts per minute (CPM) from tissues of treated mice by those from controls. In a representative experiment, increased BSA Ex was noted in the lungs of mice treated with IL-2 when compared with HBSS (6187 +/- 141 and 638 +/- 64 CPM +/- SEM, respectively; p2 < .001; PI = 9.7). Other tissues with increased BSA Ex included the liver, spleen, kidneys and mesenteric lymph nodes (PI = 6.7, 10.0, 6.3, 6.0, respectively). BSA Ex, which did not occur with the excipient control, was dependent upon the dose and the duration of IL-2. Serial lung weights showed dramatic increases in water weight induced by IL-2. Treatment of mice with radiation (500R), cyclophosphamide, or cortisone acetate significantly reduced IL-2 mediated BSA Ex. Thus, IL-2 induced a generalized CLS which is mediated directly or indirectly by cellular mechanisms.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 5318614
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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560152 -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALBUMINS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CATTLE
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
EDEMA
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IRRADIATION
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LEUKOCYTES
LUNGS
LYMPH NODES
LYMPHATIC SYSTEM
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MICE
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PERMEABILITY
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
RUMINANTS
SOMATIC CELLS
SPLEEN
SYMPTOMS
TRACER TECHNIQUES
VERTEBRATES
WEIGHT