Administration of high-dose intact immunoglobulin has an anti-resorption effect in a mouse model of reproductive failure

Mol Hum Reprod. 2007 Nov;13(11):807-14. doi: 10.1093/molehr/gam061. Epub 2007 Aug 31.

Abstract

Administration of high-dose intact human immunoglobulin (IH-Ig) has been applied to treat a variety of inflammatory and autoimmune diseases, and is expected to have beneficial effects on human fecundity. In the present study, we investigated whether Ig had anti-resorption effects using polyinosinic-polycytidylic acid sodium salt [poly (I:C)]-induced enhancement of fetal resorption in the mating of CBA/J x DBA/2J resorption-prone mouse model. Furthermore, we investigated the mechanism of the effect by examining the mRNA expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-10, IL-4 and TGF-beta(1) in spleens and placentas from the resorption-prone model treated with IH-Ig, by reverse transcription (RT)-polymerase chain reaction (PCR). Administration of high-dose IH-Ig significantly reduced the fetal resorption rate from 55% to 10%. This anti-resorption effect, however, was not detected in mice administered with Fab fragments of human Ig. We then performed adoptive transfer experiments to examine whether cellular components could transfer the effect. A remarkable anti-resorption effect was seen in poly (I:C)-injected pregnant recipients transferred with spleen cells from IH-Ig-treated donor mice. The RT-PCR study showed that IH-Ig reduced the expression of IFN-gamma and TNF-alpha mRNA in placentas of poly (I:C)-injected pregnant mice. The present findings demonstrate that intact Ig, particularly its Fc portion, possesses anti-resorption activity. The effect might be attributed to the suppressed production of pro-inflammatory cytokines at the maternofetal interface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fetal Resorption / prevention & control*
  • Flow Cytometry
  • Fluoresceins / pharmacology
  • Gene Expression / drug effects
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / pharmacology
  • Immunoglobulins / administration & dosage
  • Immunoglobulins / pharmacology*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Male
  • Mice
  • Placenta / drug effects
  • Placenta / metabolism
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Fluoresceins
  • Immunoglobulin G
  • Immunoglobulins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • carboxyfluoresceindiacetate
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma