Intra-amniotic administration of E coli lipopolysaccharides causes sustained inflammation of the fetal skin in sheep.

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 1ß, 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.

Inflammation of the fetal ovine skin following in utero exposure to Ureaplasma parvum.

There is increasing evidence linking in utero infection and inflammation to preterm birth. Many commensal urogenital tract microorganisms, including the Mycoplasmas and Ureaplasmas, are commonly detected in association with preterm birth. Using an ovine model of sterile fetal inflammation, we demonstrated previously that the fetal skin generates a robust inflammatory response following in utero exposure to lipopolysaccharides from Escherichia coli. The fetal skin's response to colonization of the amniotic fluid by viable microorganisms remains unstudied. We hypothesised that in utero infection with Ureaplasma parvum serovar 3 would induce a proinflammatory response in the fetal skin. We found that (1) cultured fetal keratinocytes (the primary cellular constituent of the epidermis) respond to U. parvum exposure in vitro by increasing the expression of the chemotactant monocyte chemoattractant protein 1 (MCP-1) but not interleukin 1ß (IL-1ß), IL-6, IL-8, or tumor necrosis factor-α (TNF-α); (2) the fetal skin's response to 7 days of U. parvum exposure is characterized by elevated expression of MCP-1, TNF-α, and IL-10; and (3) the magnitude of inflammatory cytokine/chemokine expression in the fetal skin is dependent on the duration of U parvum exposure. These novel findings provide further support for the role of the fetal skin in the development of fetal inflammation and the preterm birth that may follow.

Dendritic cell component in fetal dermatitis.

Fetal dermatitis (FD) has been proposed as the cutaneous counterpart of chorioamnionitis. One of its main characteristics is the expression by the inflammatory cells of Toll-like receptors (TLR). Antigen-presenter cells, such as histiocytes, neutrophils and dendritic cells usually express the latter. Histiocytes as well as neutrophils have been demonstrated in the inflammatory infiltrate of FD, but no studies have been performed about dendritic cells. Our objective is to study the population of dendritic cells in cases of FD. We have studied three cases of FD by immunohistochemistry with CD1a antibody. Dendritic cells were present in the dermis as well as in the epidermis of all the cases of FD. Nevertheless, they did not seem to be greater in number from what is considered as normal in a dermis without inflammation. Although our results are not incompatible with a main role of dendritic cells in FD, at least such a role would be plaid without an increase in the number of dendritic cells.