Preterm birth is associated with in utero infection and inflammation. Although the fetal membranes and fetus contribute to the intra-amniotic inflammatory profile, the relationships between a proinflammatory exposure to the fetal compartment and cytokine expression in the fetal skin are unknown. Using an ovine model, we asked whether the fetal skin would generate an extended response to inflammatory stimuli. Relative to control, intra-amniotic lipopolysaccharide (LPS) induced significant increases in cytokine/chemokine (interleukin 1β, IL-8, tumor necrosis factor-α, and monocyte chemoattractant protein 1) expression in skin that lasted for at least 15 days. Histological analysis demonstrated inflammatory cell infiltration in skin between 2 days and 15 days post-LPS exposure. In contrast to the fetal lung, the fetal skin continues to express proinflammatory cytokines for at least 15 days after exposure to LPS. These novel data suggest that the fetal skin may cause prolonged in utero inflammatory response causally associated with preterm birth.
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