Is interleukin-3 important in antiphospholipid antibody-mediated pregnancy failure?☆

Abstract 

Objective: To investigate the effect of interleukin-3 (IL-3) on trophoblast proliferation and expression of β₂-glycoprotein I.

Design: In vitro cell culture using primary trophoblasts and the cell lines Jeg-3, Jar, and BeWo.

Setting: Department of Obstetrics and Gynaecology, University of Auckland.

Patient(s): Women with normal pregnancies.

Intervention(s): Increasing amounts of IL-3 were added to cultures of primary human trophoblasts, cell lines, or cells treated with a proliferation inhibiting antiphospholipid-like antibody. RNA was extracted from primary human trophoblasts or cell lines.

Main Outcome Measure(s): We examined basal and IL-3-stimulated cellular proliferation by [³H] thymidine incorporation assay and secretion of β₂-glycoprotein I into culture medium by semiquantative immunoblot analysis. Reverse transcriptase-polymerase chain reaction analysis was used to demonstrate the presence of IL-3 receptor transcripts.

Result(s): The IL-3 treatment did not induce proliferation of highly purified primary trophoblast cultures or cell lines but did induce proliferation of contaminating CD45⁺ cells in trophoblast cultures. The IL-3 did not overcome the antiproliferative effect of an antiphospholipid-like monoclonal antibody on trophoblast. Secretion of β₂-glycoprotein I by trophoblast cultures was time dependent but unaltered by IL-3 treatment.

Conclusion(s): Our results question the proposed importance of IL-3 in antiphospholipid antibody-mediated fetal death.

Keywords:  Antiphospholipid antibodies, β₂-glycoprotein I, interleukin-3, stillbirth, miscarriage, trophoblast