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INVOLVEMENT OF INTERLEUKIN-6 IN PATHOGENESIS OF SCHIZOPHRENIA

Research Project

Project/Area Number 03807071
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionKeio University School of Medicine

Principal Investigator

YAGI Gohei  KEIO UNIVERSITY School of MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (10191082)

Co-Investigator(Kenkyū-buntansha) KINOSHITA Norihisa  KEIO UNIVERSITY School of MEDICINE,CLINICAL ASSISTANT, 医学部, 助手 (60204947)
KANBA Shigenobu  KEIO UNIVERSITY School of MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (50195187)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
KeywordsSCHIZOPHRENIA / INTERLEUKIN 1 / INTERLEUKIN 6 / STRESS / PSYCHOIMMUNOLOGY / AUTOIMMUNITY / MONOAMINE / ACTH / セロトニン / インタ-ロイキン6 / 自己免疫疾患
Research Abstract

We examined serum interleukin-6 (IL-6) in 90 schizophrenic patients in remission and 90 normal controls using enzyme-linked immuno-sorbent assay (ELISA). We found significant difference in variation between the schizophrenic and the control groups (F=10.9, P<.002). The difference in distribution was also statistically significant by Kolmogorov-Smirnov (chi-square=45.0, P<.001). Eight patients had the aberrantly high serum level of interleukin-6. Similarly, the higher level of IL-6 is characteristically found in several autoimmune disorders. This finding suggests that autoimmunity may be associated with pathogenesis of schizophrenia.
We investigated the effects of interleukin-1b (IL-1b), administered directly into the rat anterior hypothalamus (AHY), on monoamine release in the same region by using a brain microdialysis technique and a high performance liquid chromatography (HPLC)-electrochemical detection (ECD) system. First, to study the local effects of IL-1b, we used a microdialysis … More probe equipped with a microinjection tube for administering IL-1b in the same region into which the probe had been inserted. IL-1b (1 ng) injected directly into the AHY elicited release of norepinephrine (NE), dopamine (DA) and 5-hydroxytrytamine (5-HT), as well as increases in their metabolites, 4-hydroxy-3-methoxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxy-phenylacetic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA) in the AHY.Vehicle alone exerted no effect on monoamine release. Although the elevated levels of NE and DA persisted for more than 6 hr after injection of IL-1b, the elevated levels of 5-HT were transient. Second, in order to investigate whether this effect of IL-1b is a direct action in the AHY,we performed in vitro experiments using hypothalamus slices. IL-1b (0.1 and 1 nM) increased the levels of each monoamine released from hypothalamic slices in a dose-dependent manner. These findings suggest that IL-1b acts directly on the hypothalamus to induce release of NE,DA and 5-HT.Third, the roles of prostaglandins (PGs) in NE release in the AHY elicited by direct injection of IL-1b were examined. Indomethacin (INDO ; 5mg/kg) was administered intraperitoneally, then one hour later, IL-1b (1 ng) was injected directly into the AHY through the microinjection tube. IL-1b was still capable of increasing NE release, although the INDO pretreatment had decreased 6-ketoprostaglandin F1a levels in the rat hypothalamus. Fourth, to exclude the possibility that corticotropin releasing hormone (CRH) is involved in NE release by IL-1b, rats were pretreated with dexamethasone (DXM ; 0.3mg/kg), then NE release in the AHY elicited by IL-1b was measured. IL-1b was still capable of inducing NE release, although the DXM pretreatment had decreased blood adrenocorticotropic hormone (ACTH) levels. These findings suggest that IL-1b acts directly on the AHY to augment the release of NE without PG involvement or elevation of CRH levels. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Shintani,F.et al: "Interleukin 1β augments release of noreplnephrine,dopamine,and serotonin in the rat anterior hypothalamus" J.Neurosience. 13(8). 3574-3581 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shintani,F.et al: "Serum Interleukin-6 in Schizophrenic patieuts" Life Sciences. 49. 661-664 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 八木剛平: "精神分裂病の病態形成におけるインターロイキン6の関与について" 八木剛平, 1-14 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shintani,F.et al.: "Interleukin 1B augments release of norepinephrine,dopamine,and serotonin in the rat anterior hypothalamus" J.Neuroscience. 13(8). 3574-3581 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 新谷 太: "精神分裂病患者の血清インターロイキン6(IL-6)濃度" 神経化学. 34. 235-236 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 新谷 太: "精神分裂病者の血清インターロイキン6(IL-6)濃度:ELISAによるIL-6の測定" 脳と精神の医学. 2. 747-750 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shintani,F.: "Serum interleukin-6(IL-6) in schizopherenic patients:establishment of IL-6 measurement with ELISA" Life Sciences. 49. 661-664 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 新谷 太: "精神神経免疫学:内因性精神病の免疫学的研究をめぐって" 脳と精神の医学. 3. 73-80 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 新谷 太: "精神分裂病患者の血清インタ-ロイキンー6(ILー6)濃度" 神経化学. 34. 235-236 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 新谷 太: "精神分裂病者の血清インタ-ロイキンー6(ILー6)濃度:ELISAによるILー6の測定" 脳と精神の医学. 2. 747-750 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shintani F.: "Serum interleukinー6(ILー6)in schizophrenic patients: establishment of ILー6 measurement with ELISA" Life Sciences. 49. 661-664 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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