1993 Fiscal Year Final Research Report Summary
INVOLVEMENT OF INTERLEUKIN-6 IN PATHOGENESIS OF SCHIZOPHRENIA
| Project/Area Number |
03807071
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Keio 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
|
| Keywords | SCHIZOPHRENIA / INTERLEUKIN 1 / INTERLEUKIN 6 / STRESS / PSYCHOIMMUNOLOGY / AUTOIMMUNITY / MONOAMINE / ACTH |
|---|
| 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
|
Research Products
(3 results)
