Immune function in mice exposed to the adenosine deaminase inhibitor 2'-deoxycoformycin during immune system development.

Abstract

Pregnant mice were administered 2'-deoxycoformycin (2dCF), a potent inhibitor of adenosine deaminase activity, by intraperitoneal injection on day 7 or 15 of gestation or from day 8-12 or 14-18 of gestation. A total dose of 0.5 or 2.0 micrograms 2dCF/g of maternal body weight was given to the dams. In a separate study, pups born to nontreated dams were given 5 intraperitoneal injections totaling 0.5, 2.0 or 4.0 micrograms 2dCF/g beginning at 4 weeks of age. Administered doses of 2dCF were at levels known to profoundly suppress adenosine deaminase levels in adult mice. Pups born to dams injected with 2dCF from day 14-18 all died within 48 h of birth whereas other injection schedules had no effect on birth rate or survival of pups. In utero 2dCF exposure had little effect on immune function in offspring. On the other hand, body, spleen and thymus weight, and splenic cellularity were decreased in weanling mice 24 h after the last injection of 4 micrograms/g 2dCF. Proliferative responses of splenocytes to T cell mitogens and alloantigens were likewise suppressed at both 2.0 and 4.0 micrograms/g 2dCF. Suppression of proliferative responses in treated weanling mice were no longer apparent at 7 weeks of age although splenic cellularity and weight remained lower than control values. These results are similar to those we have reported for 8 week old mice given similar doses of 2dCF, with the exception of elevated levels of NK cell activity in older 2dCF-treated mice and suggest that there may be age-related differences in the sensitivity of certain cell populations to the effects of 2dCF.