Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep

OBJECTIVE: We hypothesized that fetal innate immune responses to lipopolysaccharide-induced chorioamnionitis would alter postnatal systemic immune and airway responsiveness. STUDY DESIGN: Ewes received intraamniotic injections with saline or lipopolysaccharide at 90, 100, and 110 days of gestation. Immune status and airway responsiveness were evaluated at term and at 7 weeks of age. RESULTS: At term, lymphocytes, monocytes, and neutrophils were significantly increased (respectively, 24-fold, 127-fold, and 31,000-fold) in lungs and blood monocytes became Toll-like receptor 2 responsive after lipopolysaccharide exposures. Furthermore, CD4 and CD4/CD25 lymphocytes were increased in thymus and lymph nodes. At 7 weeks, airway reactivity decreased and concentrations of CD8 cytotoxic T lymphocytes changed in the lungs and thymus relative to controls. CONCLUSION: Early gestational lipopolysaccharide exposure increased leukocyte responsiveness at term. Decreased airway reactivity and changes in lymphocytes at 7 weeks postnatal demonstrate persistent effects of fetal exposure to LPS.