Abnormal thymus development and impaired function of the immune system in rats after prenatal exposure to aciclovir

Aciclovir (synonym: acyclovir) causes abnormal thymus development in rats. After treatment on day 10 of gestation a weight reduction of the organ is obvious in 21-day-old fetuses which persists postnatally. Adult male rats exposed in utero to one or three injections of 100 mg aciclovir/kg body wt given to the dam on day 10 of pregnancy showed a reduction of the thymus weight to 333±158 mg and 276±61 mg (control: 428±92 mg;n=10). Corresponding alterations were detectable in female offspring. Liver weight was also decreased and spleen weight (in relation to body wt) was significantly increased in the offspring after the three exposures. In a host resistance model withTrichinella spiralis the function of the immune system of rats prenatally exposed to aciclovir was examined. Six weeks postnatally 10–12 randomly selected male rat offspring of one control and two treatment groups (1 or 3 injections of 100 mg aciclovir/kg body wt on day 10 of gestation) were infected orally with 500Trichinella spiralis muscle larvae. Before and several times after the infection blood was taken from a tail vein or obtained by decapitation for examination of the antibody titers (IgM, IgG, IgA, IgE) to antigens ofT. spiralis. Six weeks after the infection the weight of relevant organs was determined and tongue preparations were used forT. spiralis muscle larvae counting. Aciclovir exposed animals showed a different immune response than control rats. IgM titers in both treatment groups werehigher than in controls two weeks after the infection but not different by the end of the experiment. The IgG and IgE titers in the high dose group werelower than in the other groups at the end of the observation period. IgA antibody titers in the high dose group were alsolower than controls, but only 2 weeks after the infection. The number ofT. spiralis muscle larvae in tongue preparations was higher in the 3×100 mg aciclovir group than in the low dose group or in controls. Our results indicate that morphological thymus alterations and functional deficits of the immune system can be induced by prenatal exposure of rats to aciclovir on day 10 of gestation.