Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82).
A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects.
Department of Medical Microbiology, Lund University, Sweden.
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Truedsson
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Geborek
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Sturfelt
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D017705:Lignans; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
C059428:CPH 82; D006027:Glycosides; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D017705:Lignans; D010835:Phytohemagglutinins; D010936:Plant Extracts; D011043:Pokeweed Mitogens; D014316:Tritium; D003208:Concanavalin A; D004247:DNA; D011034:Podophyllotoxin; D013936:Thymidine