Administration of high-dose intact immunoglobulin has an anti-resorption effect in a mouse model of reproductive failure.
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.
Takeda
Masamitsu
M
Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido, Japan.
Yamada
Hideto
H
Iwabuchi
Kazuya
K
Shimada
Shigeki
S
Naito
Makoto
M
Sakuragi
Noriaki
N
Minakami
Hisanori
H
Onoé
Kazunori
K
D000818:Animals; D005260:Female; D005327:Fetal Resorption / Q000517:prevention & control*; D005434:Flow Cytometry; D005452:Fluoresceins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D007136:Immunoglobulins / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D005452:Fluoresceins; D007074:Immunoglobulin G; D007136:Immunoglobulins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C027780:carboxyfluoresceindiacetate; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma