Mol. Hum. Reprod. Advance Access published online on August 31, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam061
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Administration of high-dose intact immunoglobulin has an anti-resorption effect in a mouse model of reproductive failure
1Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan 2Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan 3 The Scripps Research Institute, La Jolla, California, USA 4Department of Cellular Function, Division of Cellular and Moleculer Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Address correspondence and reprint requests to Kazunori Onoé, Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido, Japan. E-mail: kazunori{at}igm.hokudai.ac.jp
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 IFN-
, TNF-
, IL-10, IL-4, and TGF-ß1 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- and TNF- 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.
Key Words: immunoglobulin/fetal resorption/spleen/mouse model
Submitted on July 3, 2007; resubmitted on August 14, 2007; accepted on August 21, 2007.