2002 Fiscal Year Annual Research Report

生殖現象とサイトカインクロストーク-神経-免疫-内分泌相関からの検討-

Research Project

Project/Area Number	13470347
Research Institution	Toyama Medical and Pharmaceutical University
Principal Investigator	斎藤滋富山医科薬科大学, 医学部, 教授 (30175351)
Co-Investigator(Kenkyū-buntansha)	種部恭子富山医科薬科大学, 医学部, 助手 (90303239) 酒井正利富山医科薬科大学, 付属病院, 講師 (90242502) 西条寿夫富山医科薬科大学, 医学部, 教授 (00189284)
Keywords	免疫 / サイトカイン / 生殖 / 妊娠 / 流産 / 早産 / 妊娠中毒症
Research Abstract	社会的にも小子小産が問題となる中で、現代社会の抱えるストレスによる月経不順、不妊、流産および新生児死亡の70%を占める早産、母体死亡や新生児死亡の主要因である妊娠中毒症をサイトカインの立場から検討した。その結果、common γ鎖欠損マウスでは性周期が不順となり、性周期にcommon γ鎖を受容体とするIL-2、IL-4、IL-9、IL-15、IL-21が性周期に何らかの役割を果たすことを指摘し得た。今後は視床下部周辺での、これらサイトカイン発現マップを作製する必要があると考えられた。正常妊娠例では着床部にTh2細胞の集簇が認められることを初めて証明した。またこの集簇にプロスタグランディン(PG)D_2が関与することを指摘し得た。さらに習慣流産例において胎児染色体異常例では着床部にTh2細胞は集簇しているが、胎児染色体異常例ではTh2細胞の集籏が認められないことを示した。これは母体免疫系が流産を引き起こすことを明確にした初めての報告である。さらに習慣流産例の非妊時子宮内膜にはTh2細胞の異常は認められないことから、着床期から妊娠初期にかけての母体免疫反応の異常が流産を引き起こすことを指摘しえた。妊娠中毒症においては、Th2免疫が減弱し、Th1免疫が優位となることを初めて明らかにし、その機序として末梢単球の活性化と、それに伴うIL-12産生の亢進を指摘しえた。現在、妊娠マウスにTh1細胞を輸注することで高血圧、蛋白尿を呈するモデルを完成したので、抗サイトカイン療法を用いた新たな妊娠中毒症治療法の開発を行なっている。早産においては、頚管中IL-8を指標とした頚管炎治療を妊娠20-28週(12,460例)に行い、早産が1/2に減少することを大規模臨床試験で初めて証明した。また羊水中のIL-8値と妊娠延長期間が負の相関を示し、炎症反応、サイトカインと早産の関与を明確にしえた。また胎児に炎症が波及すると脳性麻痺、慢性肺疾愚が増加することを見い出した。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Michimata T. et al.: "Accumulation of CRTH2 positive Th2 and Tc2 cells at implantation sites of human decidua in a prostaglandin D_2-mediated manner"Mol. Hum. Reprod.. 8. 181-187 (2002)
[Publications] Miyazaki S. et al.: "Interleukin 2 receptor gammachain (Υc) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise"Am. J. Reprod. Immunol.. 47. 222-230 (2002)
[Publications] Michimata T. et al.: "Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome followings recurrent abortion"Am. J. Reprod. Immunol.. 47. 196-202 (2002)
[Publications] Saito S. et al.: "Prostaglandin D_2 and reproduction"Am. J. Reprod. Immunol.. 47. 295-302 (2002)
[Publications] Sakai M. et al.: "Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients"Am. J. Reprod. Immunol.. 47. 91-97 (2002)
[Publications] Tsuda H. et al.: "A Th2 chemokine, TARC, produced by trophoblasts and endometrial gland cells, regulates the infiltration of CCR4+ T lymphocytes into human decidua at early pregnancy"Am. J. Reprod. Immunol.. 48. 1-8 (2002)
[Publications] Nishijo M. et al.: "Effects of maternal exposure to cadmium on pregnancy outcome and breast milk"Occupational & Environmental Medicine. 59. 394-397 (2002)
[Publications] Shiozaki A. et al.: "Survivin Inhibits Apotosis in Cytotrophoblasts"Placenta. 24巻1号. 65-76 (2003)
[Publications] Sakai M. et al.: "The preterm labor index and fetal fibronectin for prediction of preterm delivery with intact membranes"Obstet. Gynecol.. 101巻1号. 123-128 (2003)
[Publications] Saito S. et al.: "Th1/Th2 balance in preeclampsia"J. Reprod. Immunol.. (in press).
[Publications] Michimata T. et al.: "T-helper 2 cells and T-cytotoxic 2 cells at implantation sites decrease in unexplained recurrent spontaneous abortion with normal chromosomal content"Hum. Reprod.. (in press).
[Publications] Hori E.et al.: "Effects of a novel arginine-vasopressin derivative, NC-1900, on the spatial memory impairment of rats with transient forebrain ischemia"Cognitive Brain Res. 13. 1-15 (2002)
[Publications] Toyomitsu Y. et al.: "Neuronal responses of the rat amygdala during extinction and reassociation learning in the elementary and configural associative tasks"Eur. J Neurosci.. 15. 753-768 (2002)
[Publications] Kobayashi T. et al.: "Contribution of hippocampal place cell activity to learning and formation of goal-directed navigation in rats"Neuroscience. (in press).
[Publications] Takakura H. et al.: "Differential activation in the medial temporal lobe during a sound-sequence discrimination task across age in human subjects"Neuroscience. (in press).
[Publications] Umeno K. et al.: "Gamma-band EEGs predict autonomic responses during mental arithmetic"NeuroReport. (in press).
[Publications] 斎藤滋編集:谷口克, 宮坂昌之: "標準免疫学"医学書院. 1-522 (2002)

2002 Fiscal Year Annual Research Report

生殖現象とサイトカインクロストーク-神経-免疫-内分泌相関からの検討-

Principal Investigator

斎藤 滋 富山医科薬科大学, 医学部, 教授 (30175351)

Research Products

[Publications] Michimata T. et al.: "Accumulation of CRTH2 positive Th2 and Tc2 cells at implantation sites of human decidua in a prostaglandin D_2-mediated manner"Mol. Hum. Reprod.. 8. 181-187 (2002)

[Publications] Miyazaki S. et al.: "Interleukin 2 receptor gammachain (Υc) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise"Am. J. Reprod. Immunol.. 47. 222-230 (2002)

[Publications] Michimata T. et al.: "Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome followings recurrent abortion"Am. J. Reprod. Immunol.. 47. 196-202 (2002)

[Publications] Saito S. et al.: "Prostaglandin D_2 and reproduction"Am. J. Reprod. Immunol.. 47. 295-302 (2002)

[Publications] Sakai M. et al.: "Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients"Am. J. Reprod. Immunol.. 47. 91-97 (2002)

[Publications] Tsuda H. et al.: "A Th2 chemokine, TARC, produced by trophoblasts and endometrial gland cells, regulates the infiltration of CCR4+ T lymphocytes into human decidua at early pregnancy"Am. J. Reprod. Immunol.. 48. 1-8 (2002)

[Publications] Nishijo M. et al.: "Effects of maternal exposure to cadmium on pregnancy outcome and breast milk"Occupational & Environmental Medicine. 59. 394-397 (2002)

[Publications] Shiozaki A. et al.: "Survivin Inhibits Apotosis in Cytotrophoblasts"Placenta. 24巻1号. 65-76 (2003)

[Publications] Sakai M. et al.: "The preterm labor index and fetal fibronectin for prediction of preterm delivery with intact membranes"Obstet. Gynecol.. 101巻1号. 123-128 (2003)

[Publications] Saito S. et al.: "Th1/Th2 balance in preeclampsia"J. Reprod. Immunol.. (in press).

[Publications] Michimata T. et al.: "T-helper 2 cells and T-cytotoxic 2 cells at implantation sites decrease in unexplained recurrent spontaneous abortion with normal chromosomal content"Hum. Reprod.. (in press).

[Publications] Hori E.et al.: "Effects of a novel arginine-vasopressin derivative, NC-1900, on the spatial memory impairment of rats with transient forebrain ischemia"Cognitive Brain Res. 13. 1-15 (2002)

[Publications] Toyomitsu Y. et al.: "Neuronal responses of the rat amygdala during extinction and reassociation learning in the elementary and configural associative tasks"Eur. J Neurosci.. 15. 753-768 (2002)

[Publications] Kobayashi T. et al.: "Contribution of hippocampal place cell activity to learning and formation of goal-directed navigation in rats"Neuroscience. (in press).

[Publications] Takakura H. et al.: "Differential activation in the medial temporal lobe during a sound-sequence discrimination task across age in human subjects"Neuroscience. (in press).

[Publications] Umeno K. et al.: "Gamma-band EEGs predict autonomic responses during mental arithmetic"NeuroReport. (in press).

[Publications] 斎藤 滋 編集:谷口 克, 宮坂 昌之: "標準免疫学"医学書院. 1-522 (2002)

斎藤滋富山医科薬科大学, 医学部, 教授 (30175351)

[Publications] 斎藤滋編集:谷口克, 宮坂昌之: "標準免疫学"医学書院. 1-522 (2002)