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Effects of Interleukin-12 Administration during the Pre- and Peri-Implantation Period on Mouse Embryofetal Development


Address reprint requests to Dr Anna Maria Di Blasio, Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18 - Cusano Milanino, Milan, Italy.


Problem:  The immunological success of pregnancy is thought to depend upon the establishment of a balance between favorable and deleterious cytokines, the current paradigm viewing pregnancy as a T helper (Th)2 cytokine-dependent phenomenon. In this context, a particular attention should be directed to the potential role of interleukin (IL)-12, which promotes the development of Th1 responses, in the induction of adverse pregnancy-related phenomena. Indeed, very few data linked the Th1-inducer IL-12 to the event of abortion.

Methods:  In this study, we have investigated the maternal and fetal effects of exogenous administration of IL-12 to CD1 (BR) ICR mice during the pre- and peri-implantation period (day 2–6 of pregnancy). Animals have been evaluated for parameters of reproductive performance, embryo and fetal developmental toxicity and maternal toxicity.

Results:  Intraperitoneal administration of IL-12 at concentrations from 2.5 to 10 μg/kg daily did not result in an increase in the murine abortion rate. A statistically significant, although minimal, decrease in the number of somites were found in the embryos of animals treated with IL-12 at a dose of 10 μg/kg/day. However, developmental parameters at birth were similar between the two groups of animals suggesting that alteration of somites might be a transitory state during treatment. An increased body weight gains and reduced feed and water consumption were observed in the mothers treated with the cytokine.

Conclusion:  In the present experimental conditions and in this specific strain of mice, IL-12 does not exert adverse effects on reproductive performance and induces an only modest harmful action on mothers and embryos.