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Interleukin‐1 beta production in the rabbit brain during endotoxin‐induced fever.
Author(s) -
Nakamori T,
Morimoto A,
Yamaguchi K,
Watanabe T,
Murakami N
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp020121
Subject(s) - lipopolysaccharide , parenchyma , beta (programming language) , endocrinology , medicine , spleen , prostaglandin e2 , microgram , pharmacology , chemistry , biology , pathology , in vitro , biochemistry , computer science , programming language
Interleukin‐1 beta (IL‐1 beta) production in the brain and the spleen was investigated in rabbits made febrile by intravenous (I.V.) injection of endotoxin, or human recombinant IL‐1 beta (hIL‐1 beta). The endotoxin used in the present study was the lipopolysaccharide (LPS) of Salmonella typhosa endotoxin. Monophasic fever was induced by I.V. injection of a low dose of LPS (0.02 micrograms kg‐1) and biphasic fever by I.V. injection of a large dose of LPS (4 micrograms kg‐1), a sublethal dose of LPS (40 micrograms kg‐1) or hIL‐1 beta (2 micrograms kg‐1). In situ hybridization and immunohistochemical studies revealed that, although no IL‐1 beta production was observed in the brain at 1 and 3 h after injection of a low dose of LPS (0.02 micrograms kg‐1) or of hIL‐1 beta (2 micrograms kg‐1), IL‐1 beta production was demonstrated in organum vasculosum laminae terminalis (OVLT) and some cells around the blood vessels in the parenchyma 1 h after 4 micrograms kg‐1 LPS. IL‐1 beta production was detected throughout the brain after 40 micrograms kg‐1 LPS. Pretreatment with indomethacin, an inhibitor of prostaglandin synthesis, did not affect IL‐1 beta production in the brain induced by 4 micrograms kg‐1 LPS. The cell type which produces IL‐1 beta in the OVLT following LPS injection was confirmed to be a macrophage by electron microscopy. The cells producing IL‐1 beta in the parenchyma were determined to be microglial cells. In the spleen, each dose of LPS induced a significant increase in IL‐1 beta production in polymorphonuclear cells and macrophages in the red pulp 1 h after injection. However, 2 micrograms kg‐1 hIL‐1 beta did not induce IL‐1 beta production in the spleen. The present results show clearly that systemic administration of LPS induces IL‐1 beta production in the OVLT which may be responsible for induction of the second phase of biphasic fever. The production of IL‐1 beta in the OVLT was not attributable to the action of peripherally synthesized IL‐1 beta or prostaglandins.