Effects of new antiepileptic drugs and progabide on the mitogen-induced proliferative activity of mouse splenocytes.
Classical antiepileptic drugs are known to affect immune system activity, although the effects of new generation anticonvulsants on T- and B-cell-mediated immunity remain unknown. Therefore, in the present study, we compared a selection of new antiepileptic drugs with classical ones in terms of their effects on the proliferative activity of lymphocytes stimulated by concanavalin A(Con A) and lipopolysaccharide (LPS). Felbamate (3 x 10(-6) - 10(-4) M) was the most potent in inhibiting [(3)H]-thymidine incorporation in C57BL/6 mouse spleen cells stimulated by Con A and LPS. Treatment of the cells with stiripentol (3 x 10(-5) and 10(-4) M) and loreclezole (10(-4) M) suppressed the proliferative activity of splenocytes both after Con A and LPS stimulation. Tiagabine (3 x 10(-5) M and 10(-4) M) inhibited the Con A-induced cell proliferation, whereas the effect of LPS was attenuated only by the highest concentration of this drug (10(-4) M). Progabide showed immunosuppressive effects at concentrations of 3 x 10(-5) and 10(-4) M or only 10(-4) M after LPS or Con A stimulation, respectively. No effect on the immune parameters was observed after lamotrigine treatment. On the other hand, the Con A-induced proliferation of splenocytes was enhanced by carbamazepine (10(-5) - 10(-4) M) and sodium valproate (5 x 10(-4) - 3 x 10(-3) M). Neither carbamazepine nor sodium valproate affected the LPS-induced proliferation. These data indicate that some new antiepileptic drugs, especially felbamate at pharmacological concentrations, may suppress the mitogen-stimulated proliferative activity of mouse splenocytes. In contrast, two classical anticonvulsants (carbamazepine and sodium valproate) stimulated T-cell-mediated immunity. The above differences in the effects of particular antiepileptic drugs on the immune response may play roles in both their therapeutic efficiency and undesired effects.
Basta-Kaim
Agnieszka
A
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Budziszewska
Bogusława
B
Leśkiewicz
Monika
M
Kubera
Marta
M
Jagła
Grzegorz
G
Nowak
Wojciech
W
Czuczwar
Stanisław J
SJ
Lasoń
Władysław
W
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D008934:Mitogens; C017985:progabide; D005680:gamma-Aminobutyric Acid