IN-VITRO LYMPHOTOXICITY AND SELECTIVE T-CELL IMMUNOTOXICITY OF HIGH-DOSES OF ACYCLOVIR AND ITS DERIVATIVES IN MICE

The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N-2-acetyl ACV (ac-ACV) and N-2,O-diacetyl ACV (diac-ACV) were examined for their potential i n vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro ly mphotoxicity of ACV and its acetylated derivatives was low, whereas th e 7-ACV isomer enhanced the bl vitro cell proliferation in PHA-stimula ted cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute numbe r of CD3(+), CD8(+), and CD25(+) cells, but not Ig(+) cells, was noted at high concentrations of ACV and its derivatives, suggesting a selec tive T cell cytotoxicity. Similarly, the in vivo exposure revealed sel ective T cell immunotoxicity of ACV and its derivatives since the redu ced number of Thy 1.2(+) and CD8(+) cells was not accompanied with any marked changes in the Ig(+) population. The CD4(+)/CD8(+) ratio was a ffected both in vitro and in vivo by high concentrations of ACV. Copyr ight (C) 1996 International Society for Immunopharmacology