| Project/Area Number |
62480112
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境生理学(含体力医学･栄養生理学)
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| Research Institution | Yamanashi Medical College |
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Principal Investigator |
IRIKI Masami Yamanashi Med. Coll., Dept. of Physiology, Professor, 医学部, 教授 (90072967)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Yoshiya National Inst. Radiological Sciences, Researcher, 生理病理研究部, 研究員 (10201550)
HASHIMOTO Masaaki Yamanashi Med. Coll., Dept. Physiology, Assistant, 医学部, 助手 (30156294)
NAGAI Masanori Yamanashi Med. Coll., Dept. of Physiology, Assistant Professor, 医学部, 講師 (40110027)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Tumor Necrosis, Factor(TNF) / TNFalpha / TNFbeta / Endogenous pyrogen / Fever / Fever syndrome / Regional differentiation of sympathetic efferents / 睡眠 / 発熱物質 / prostaglandin E |
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| Research Abstract |
Mechanisms of Fever induced by Tumor Necrosis Factor Masami IRIKI
Tumor necrosis factor (TNF) , one of the cytokines, has not only anti-tumor action, but also various actions including pyrogenesis. On the other hand, TNF, alike with Interleukin 1 (IL1) and Interferon, acts as endogenous pyrogen in fever induced by endotoxin or by its effective component LPS (lipopolysaccharide). They act upon thermoregulatory center via mediator, which is asserted to be PGE_2 The purpose of the studies is to elucidate the mechanisms involved in fever and fever syndrome (host defense responses including fever) induced by TNF. The results obtained can be summarized as follows.
1. TNF is pyrogenic. Intravenous (iv) or intracerebro-ventricular (icv) injection of TNF, induced monophasic fever at low doses and biphasic fever at high doses.
2. TNF participates in LPS fever. TNF activity in blood increased transiently after LPS administration, and the second peak of LPS fever was inhibited by TNF antibody.
3. In the central mechanisms of TNF fever, different from that of IL1 fever, the factors other than arachidonic acid metabolites can act as mediators. Fever induced by iv or icv injection of TNF was not be inhibited by subcutaneous or icv injection of indomethacin, an arachidonic metabolite inhibitor.
4. The effect of TNF on fever syndrome can be the same as or different from that of IL1 according to the sort of responses: The pattern of the regional differentiation of sympathetic efferents induced by TNF was the same as that induced by IL1. However, the effect of TNF on the sleep pattern was different from that of IL1.
5. There was no significant difference between the pyrogenic effect of TNFAalpha (cytokines) and that of TNFbeta (lymphokines).
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