ANTIPROLIFERATIVE EFFECTS ON HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLSAND INHIBITION OF INVITRO IMMUNOGLOBULIN-SYNTHESIS BY PODOPHYLLOTOXIN(CPH86) AND BY SEMISYNTHETIC LIGNAN GLYCOSIDES (CPH82)

A mixture of natural and semisynthetic (modified) glycosides from Podo phyllum 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 preparatio n containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs w ere shown to inhibit in vitro [H-3]-thymidine uptake of human peripher al blood mononuclear cells stimulated by the mitogens concanavallin A, phythaemagglutinin and pokeweed mitogen. Complete inhibition was obse rved with CPH86 in concentrations greater-than-or-equal-to 20 ng/ml an d with CPH82 in concentrations greater-than-or-equal-to 1 mug/ml. In v itro production of IgG, IgM and IgA by PWM-stimulated cells cultured f or 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but wa s strongly inhibited by concentrations of CPH86 at greater-than-or-equ al-to 20 ng/ml and CPH82 at greater-than-or-equal-to 1 mug/ml. In conc lusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte prolif eration and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects.