Changes in blood cytokine levels under stress conditions and their application to forensic diagnosis.

2009 Fiscal Year Final Research Report

• Project/Area Number: 19590684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: TOMITA Masafumi Kawasaki Medical School, 医学部, 准教授 (50113197)
• Co-Investigator(Kenkyū-buntansha): KATSUYAMA Hironobu 川崎医科大学, 医学部, 教授 (00289175) ; HIDAKA Kazuo 川崎医科大学, 医学部, 准教授 (00069064) ; WATANABE Yoko 川崎医科大学, 医学部, 助教 (70135945)
• Research Collaborator: OKUYAMA Toshiko 川崎医科大学, 医学部, 研究補助員
• Project Period (FY): 2007 – 2009
• Keywords: 中毒 / ストレス / サイトカイン / 覚せい剤 / パラコート / 遺伝子

Research Abstract

The cytokines investigated were IFN-γ, IL-6, IL-10, IL-12p70, MCP-1 and TNF. First, we investigated the effect of paraquat (Pq) on cytokine levels using the model of Pq-poisoned mice. As the result, IL-6 and MCP-1 levels, both mRNA in tissues and protein levels in blood, significantly increased within 5 days after Pq exposure. The former may be an early marker and the latter be a late marker for lung acute damage. Now we examine the effect of anti IL-6 antibody to Pq-poisoned damage, which need further investigation. Next, we examined the effects of methamphetamine (MA) on cytokine levels using a water-immersion restraint stress (WRS) mouse model. The levels of the serum cytokines IL-6, IL-10 and TNF were increased by stress, and were markedly increased by MA under stress conditions ; in particular, the level of IL-6 was synergistically increased. On the other hand, MA resulted in significant suppression of the stress-induced gastric injury, although further studies are necessary to resolve the mechanism. We investigated the involvement of the GR polymorphism in stress response using ICR mice. Our results suggest that the GR gene polymorphism has a significant impact on the stress-induced output, including cytokines, corticosterone, Hsp70 levels in serum, and the gastric lesion index. These studies provide insights into the role of GR in individual responses to stress.

Research Products

• [Journal Article] The effect of CAG repeat polymorphism in the glucocorticoid receptor on stress responses of mice exposed to waterimmersion restraint stress. (2010)
  • Author(s): Tomita M, Katsuyama H, Okuyama T, Watanabe Y, Hidaka K, Otsuki T, Nata M
  • Journal Title: Int. J. Mol. Med. 25(3) Pages: 415-420
  • Peer Reviewed
• [Journal Article] Methamphetamine protects against stress-induced gastric mucosal lesions in mice. (2009)
  • Author(s): Tomita M, Okuyama T, Katsuyama H, Watanabe Y, Hidaka K, et. al. (9人)
  • Journal Title: Legal Med. (Tokyo) 11(s1) Pages: S437-S439
  • Peer Reviewed
• [Journal Article] Association between serotonin transporter gene polymorphisms and depressed mood caused by job stress in Japanese workers. (2008)
  • Author(s): Katsuyama H, Tomita M, Hidaka K, Watanabe Y, et. al. (10人:2番目)
  • Journal Title: Int. J. Mol. Med. 21(4) Pages: 499-505
  • Peer Reviewed
• [Presentation] A polymorphism in the glucocorticoid receptor gene is associated with responses of mice exposed to stress (2009)
  • Author(s): Tomita Masafumi, et al.
  • Organizer: The 4th International Congress on Stress Responses in Biology and Medicine.
  • Year and Date: 20090000
• [Presentation] マウスでのストレス感受性とグルココルチコイドレセプター多型の関連 (2009)
  • Author(s): 富田正文, 他
  • Organizer: 日本DNA多型学会
  • Place of Presentation: 久留米
  • Year and Date: 2009-11-20
• [Presentation] グルココルチコイドレセプター(GR)遺伝子多型とストレス性胃内出血に関連性はあるのか? (2009)
  • Author(s): 富田正文, 他
  • Organizer: 第93次日本法医学会学術全国集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-14
• [Presentation] 覚醒剤及び身体拘束の心臓における遺伝子発現への影響 (2009)
  • Author(s): 篠根光太郎, 富田正文, 他
  • Organizer: (第2報)第93次日本法医学会学術全国集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-14
• [Presentation] メタンフェタミンによる血中サイトカインレベルの変化-ストレスによる影響について- (2008)
  • Author(s): 富田正文, 他
  • Organizer: 第35回日本トキシコロジー学会学術年会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-27
• [Presentation] 水浸拘束stressにおける血中サイトカインレベルに及ぼすメタンフェタミンの影響 (2008)
  • Author(s): 富田正文, 他
  • Organizer: 第92次日本法医学会学術全国集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-04-24
• [Presentation] マウスパラコート肺モデル早期での遺伝子発現とサイトカインレベルの変化 (2007)
  • Author(s): 富田正文, 他
  • Organizer: 第34回日本トキシコロジー学会学術年会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-27
• [Presentation] パラコートによる肺destructive phaseでの遺伝子発現変化 (2007)
  • Author(s): 富田正文、石川隆紀
  • Organizer: 第91次日本法医学会学術全国集会
  • Place of Presentation: 秋田
  • Year and Date: 2007-05-16
• [Book] DNA多型 (2009)
  • Author(s): 勝山博信, 伏見滋子, 富田正文, 奥山敏子, 日高和夫, 渡辺洋子, 為近美栄
  • Total Pages: 281-283
  • Publisher: 東洋書店
• [Remarks]
  • URL: http://www.kawasaki-m.ac.jp/med/study/info.php?id=302