Placental Production of Immunoregulatory Factors: Trophoblast is a Source of Interleukin-1

Abstract

The placenta is often viewed as an immunologically passive organ either “camouflauged” to avoid immune surveillance or acting as a “sponge” to clear maternal anti-fetal antibodies. We and others have previously isolated low molecular weight lymphokines from human placental explant culture supernatants which would suggest a more active role of the placenta in modulating maternal immune responses (Lala et al., 1984). These include a 70–78 Kilodalton (KD) suppressor of IL-2 dependent cell proliferation (Main et al., 1985), and a 15–17 KD protein which on partial purification (by gel filtration and isoelectric focusing) and by biological activity is identical to adult monocyte-derived Interleukin-1 (IL-1) (Flynn et al., 1982). IL-1 is a key mediator of inflammatory responses leading to lymphocyte activation, systemic metabolic changes, elevated body temperature, local production of collagenase, and stimulation of fibroblast proliferation (Dinarello, 1984; Lachman, 1983). It is now known to be produced by a variety of cell types including monocytes, tissue fixed macrophages, keratinocytes, corneal epithelial cells, astrocytes, and renal mesangial cells. IL-1 is extraordinary potent, with biologic activity demonstrated in the 10-¹⁰M concentration range. This high specific activity has facilitated its detection in bioassays but because it is produced in such small quantities, purification and production of monoclonal antibodies has been difficult. We have measured placental IL-1 using both the mouse thymocyte assay and the newer, more sensitive IL-1 dependent tumor line assay. In this report, we address three issues: (1) Can villous tissue from early in gestation produce Interleukin-1? (2) Of the various cell types present in a human term placenta which are capable of producing IL-1? (3) How does the level of IL-1 production by placental cells compare to that produced by human peripheral blood monocytes?