The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women

J Clin Endocrinol Metab. 2000 Dec;85(12):4781-8. doi: 10.1210/jcem.85.12.7007.


Macrophage inhibitory cytokine-1 (MIC-1) is a recently described divergent member of the transforming growth factor-ss superfamily. MIC-1 transcription up-regulation is associated with macrophage activation, and this observation led to its cloning. Northern blots indicate that MIC-1 is also present in human placenta. A sensitive sandwich enzyme-linked immunosorbent assay for the quantification of MIC-1 was developed and used to examine the role of this cytokine in pregnancy. High levels of MIC-1 are present in the sera of pregnant women. The level rises substantially with progress of gestation. MIC-1 can also be detected, in large amounts, in amniotic fluid and placental extracts. In addition, the BeWo placental trophoblastic cell line was found to constitutively express the MIC-1 transcript and secrete large amounts of MIC-1. These findings suggest that the placental trophoblast is a major source of the MIC-1 present in maternal serum and amniotic fluid. We suggest that MIC-1 may promote fetal survival by suppressing the production of maternally derived proinflammatory cytokines within the uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amniotic Fluid / chemistry
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Line
  • Cytokines / blood*
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Growth Differentiation Factor 15
  • Humans
  • Immunohistochemistry
  • Mice
  • Placenta / metabolism
  • Precipitin Tests
  • Pregnancy / blood*
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep
  • Transforming Growth Factor beta / blood*
  • Trophoblasts / metabolism


  • Antibodies, Monoclonal
  • Cytokines
  • GDF15 protein, human
  • Gdf15 protein, mouse
  • Growth Differentiation Factor 15
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta