Humoral immune dysfunction as a result of prenatal exposure to diphenylhydantion: Correlation with the occurrence of physical defects

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Abstract
The effect of prenatal exposure to diphenylhydantoin (DPH) on postnatal immune function of offspring was studied using a longitudinal experimental design and in vivo immunoassays. Maternal Balb/c mice were dosed by gavage on gestation days 9 through 18 with 0, 20, 40, or 60 mg/kg DPH. Humoral immune function was assessed by measuring the serum antibody levels to type III pneumococcal polysaccharide 5 days after immunization by radioimmunoassay. Cell-mediated immune function was assessed by measuring the delayed-type hypersensitivity response to the contact allergen oxazolone using a micrometer method. A dose-related suppression of humoral immune function was observed in male and female offspring at 25 days but not at 15 weeks of age. Cell-mediated immunity was not affected by prenatal DPH exposure at 25 days or 15 weeks of age. Offspring developed purulent eye exudates at 12 days of age; the incidence and persistence was related to DPH dose. The immunosuppressive effect of DPH on humoral immune function was significantly greater in offspring born with open eye defect than in similarly treated but physically normal offspring. The results suggest that prenatal exposure to DPH may adversely affect the normal development and expression of humoral immune function, particularly in those offspring with other manifestations of DPH's developmental toxicology.