Interleukin-1 beta production in the rabbit brain during endotoxin-induced fever

J Physiol. 1994 Apr 1;476(1):177-86.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins*
  • Brain Chemistry / drug effects*
  • Cerebral Ventricles / physiology
  • Endotoxins*
  • Fever / chemically induced
  • Fever / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Indomethacin / pharmacology
  • Interleukin-1 / biosynthesis*
  • Macrophages / metabolism
  • Male
  • Microscopy, Electron
  • Plasmids
  • RNA Probes
  • Rabbits
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Salmonella typhi / metabolism*

Substances

  • Bacterial Toxins
  • Endotoxins
  • Interleukin-1
  • RNA Probes
  • Recombinant Proteins
  • salmonella toxin
  • Indomethacin