Gestational age-dependent expression of IL-10 and its receptor in human placental tissues and isolated cytotrophoblasts

Control of antifetal immune responses is thought to be regulated locally by the placenta. Because the physiologic programming of the placenta across g estation is likely to influence the local immunity, we hypothesize that a p otent anti-inflammatory cytokine such as IL-10 may be produced in a gestati onal age-dependent manner. In the present study, we examined the expression of IL-IO and its receptor in placental explants or freshly isolated cytotr ophoblasts from different gestational ages and compared it with the express ion profiles of other cytokines, First and second trimester placental tissu es from normal pregnancies predominantly expressed IL-IO, whereas the level s of IL-2, IL-4, and IFN-gamma were mostly below detection throughout pregn ancy. The expression of IL-10, but not its receptor, diminished significant ly in term placental tissues collected "before" the onset of labor and did not change appreciably "after" labor. On the other hand, TNF-alpha and IL-1 beta were significantly up-regulated in response to labor-associated condi tions. IL-10 expression was transcriptionally attenuated at term as observe d in cytotrophoblasts, In contrast to the placental cytokine milieu, autolo gous PBMCs, when activated with PHA, secreted significant amounts of IL-2, IL-4, IL-IO, and IFN-gamma, albeit with a statistically significantly enhan ced IL-10 production in first trimester compared with age-matched nonpregna nt women. These data suggest that IL-10 is expressed in the placenta in a g estational age-dependent manner and that its down-regulation at term may be an important mechanism underlying the subtle changes associated with partu rition.