Effects of cyclophosphamide on in vitro human lymphocyte culture and mitogenic stimulation
Cyclophosphamide (CY) has been reported to be inactive in vitro under certain conditions. In the present study, CY was tested for its ability to inhibit human lymphocyte proliferation and to modulate lymphocyte response to mitogens in vitro. The inhibition of or the increase in /sup 3/H-thymidine incorporation in mitogen-stimulated and unstimulated lymphocytes by CY was used as a measure of CY activity in vitro. The results demonstrate that lymphocytes from 10 different persons had a mean decrease of 74% in /sup 3/H-thymidine incorporation in the presence of CY (P less than 0.005). The effect was maximal at a concentration of 160 micrograms/ml. A mean inhibition of 35 and 55% was caused by 10 and 40 micrograms/ml concentrations of CY, respectively. CY also was able to reduce the number of viable cells during 5 days in culture and had a profound effect on mitogen stimulation of lymphocytes. In all cases, CY modulated the stimulation of lymphocytes by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) either by augmenting or suppressing the responses. At low concentrations (10 micrograms/ml) it augmented mitogenic stimulation by 46 to 281%. At higher concentrations (20 to 160 micrograms/ml), CY had a suppressive effect with a maximum suppression of 99%. The CY-induced immunomodulation is perhaps caused by its action on the regulatory T cells. When tested in vitro, CY had inhibitory activity on T cells.
- Research Organization:
- Department of Medicine, University of California, Irvine
- OSTI ID:
- 5681451
- Journal Information:
- Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 35:2; ISSN TRPLA
- Country of Publication:
- United States
- Language:
- English
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560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AGGLUTININS
ALKYLATING AGENTS
ANIMAL CELLS
ANTIBODIES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CELL CULTURES
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DRUGS
ENDOXAN
HEMAGGLUTININS
HETEROCYCLIC COMPOUNDS
IMMUNOSUPPRESSIVE DRUGS
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LYMPHOCYTES
MATERIALS
MITOGENS
MUCOPROTEINS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHYTOHEMAGGLUTININ
POLYSACCHARIDES
PROTEINS
PYRIMIDINES
RESPONSE MODIFYING FACTORS
RIBOSIDES
SACCHARIDES
SOMATIC CELLS
STIMULATION
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS