Figure 4

Summary of the effects of the PDE4 inhibition in gestational tissues in the case of intra-uterine inflammation. Intrauterine inflammation leads to massive production of cytokines and chemokines, mainly by the fetal membranes, the chorio-decidua. Cytokines and chemokines start a feedforward mechanism and the production of uterotonic agonists and metalloproteases in the chorio-decidua. These agents further digest the fetal membranes, contract the myometrium, and soften the cervix, causing preterm labor. Moreover, inflammation of the amniotic cavity may target the developing brain and lungs of the fetus. We showed that PDE4 inhibition may directly in the human myometrium and indirectly by decreasing production of cytokines in the fetal membranes diminish uterine contraction and delay preterm delivery. Furthermore, by decreasing intrauterine inflammation, PDE4 inhibitors may favor a normal development of the fetal brain and lungs.