Interleukin-1 beta production in the rabbit brain during endotoxin-induced fever.
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.
Nakamori
T
T
Department of Physiology, Yamaguchi University School of Medicine, Japan.
Morimoto
A
A
Yamaguchi
K
K
Watanabe
T
T
Murakami
N
N
D000818:Animals; D001427:Bacterial Toxins; D001923:Brain Chemistry / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000502:physiology; D004731:Endotoxins; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D010957:Plasmids; D015347:RNA Probes; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D012485:Salmonella typhi / Q000378:metabolism*
D001427:Bacterial Toxins; D004731:Endotoxins; D007375:Interleukin-1; D015347:RNA Probes; D011994:Recombinant Proteins; C027952:salmonella toxin; D007213:Indomethacin