| 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. |
| Authors | Masamitsu Takeda, Hideto Yamada, Kazuya Iwabuchi, Shigeki Shimada, Makoto Naito, Noriaki Sakuragi, Hisanori Minakami, Kazunori Onoé
(Affiliation: Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido, Japan.)
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| Journal | Molecular human reproduction
(Mol Hum Reprod)
Vol. 13
Issue 11
Pg. 807-14
(Nov 2007)
ISSN: 1460-2407 England |
| PMID | 17766682
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Fluoresceins
- Immunoglobulin G
- Immunoglobulins
- RNA, Messenger
- Transforming Growth Factor beta
- Tumor Necrosis Factor-alpha
- carboxyfluoresceindiacetate
- Interleukin-10
- Interleukin-4
- Interferon-gamma
|
| Topics |
- Animals
- Female
- Fetal Resorption
(prevention & control)
- Flow Cytometry
- Fluoresceins
(pharmacology)
- Gene Expression
(drug effects)
- Immunoglobulin G
(administration & dosage, pharmacology)
- Immunoglobulins
(administration & dosage, pharmacology)
- Interferon-gamma
(genetics, metabolism)
- Interleukin-10
(genetics, metabolism)
- Interleukin-4
(genetics, metabolism)
- Male
- Mice
- Placenta
(drug effects, metabolism)
- Pregnancy
- RNA, Messenger
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Spleen
(cytology, metabolism)
- Transforming Growth Factor beta
(genetics, metabolism)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
|
