In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice
- CBER, FDA, Bethesda, MD (USA)
We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-(125I)iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-(125I)iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice.
- OSTI ID:
- 6528824
- Journal Information:
- Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:17; ISSN CNREA; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DEOXYURIDINE
DISTRIBUTION
DNA
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VIVO
INTERFERON
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MICE
MITOGENS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RIBOSIDES
RODENTS
SOMATIC CELLS
SYNERGISM
TISSUE DISTRIBUTION
TRACER TECHNIQUES
URACILS
VERTEBRATES