ABSTRACT Non-specific stimulation of the maternal immune system during the peri-conception period has broad spectrum efficacy for reducing teratogen-induced birth defects in mice. Morphological lesions that were reduced or blocked in mice included cleft palate and associated craniofacial defects, digit and limb defects, tail malformations and neural tube defects (NTD; both exencephaly and rachyschisis). Teratogenic stimuli used to induce morphologic defects included diverse chemical agents, hyperthermia, x-rays, or diabetes mellitus. Equally diverse procedures of immune stimulation proved effective for defect reduction, including footpad injection with complete Freund’s Complete Adjuvant (FCA), intraperitoneal injection with inert particles or attenuated Bacillus Calmette-Guerin (BCG), intrauterine injection with allogenic or xenogenic lymphocytes or intravascular, intrauterine or IP injection with immunomodulatory cytokines. Limited information is available regarding mechanisms by which such immune stimulation reduces fetal dysmorphogenesis. The collective literature suggests the possibility that immunoregulatory cytokines of maternal origin may be effector molecules in this phenomenon.
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