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Elevation of interleukin-6 in response to a chronic inflammatory stimulus
in mice: inhibition by indomethacin
E Shacter, GK Arzadon and J Williams
Laboratory of Genetics, National Cancer Institute, National Institutes of
Health, Bethesda, MD 20892.
Intraperitoneal (i.p.) injection of a mineral oil such as pristane induces
a chronic inflammatory response in mice. This is characterized by a large
influx of macrophages and other inflammatory cells into the peritoneal
cavity for months after injection of the oil. By using the B9 cell
bioassay, it was found that injection of pristane caused a marked and
prolonged elevation of interleukin-6 (IL-6) levels in the peritoneal
cavities of the mice. IL-6 was undetectable (less than 15 U/mL) in the
peritoneal fluids of unprimed mice and during the first week after
injecting pristane. From 4 to 20 weeks, the concentration of IL-6 increased
to an apparent plateau with concentrations ranging from 200 to 2,000 U/mL.
Increasing the dose of pristane did not substantially increase the
peritoneal levels of IL-6 established at 20 weeks after pristane treatment.
At later times (by day 250), the level decreased to 263 +/- 217 U/mL.
However, mice that developed plasma cell tumors around day 300 showed high
levels of IL-6 in the ascites fluid (650 to 2,400 U/mL). Serum levels of
IL-6 were also elevated in pristane-primed mice but were substantially
lower than those found in the peritoneal cavity. Chronic administration of
the nonsteroidal anti- inflammatory drug indomethacin decreased the levels
of IL-6 by 75% to 80%. Experiments performed in vitro showed that
pristane-elicited macrophages secreted low levels of IL-6 constitutively
and high levels of IL-6 in the presence of lipopolysaccharide. Both IL-6
and prostaglandin E2 production were inhibited by addition of indomethacin
to macrophage cultures in vitro. Treatment of mice with pristane may
provide a model system for studying the inflammatory pathways that control
IL-6 levels in vivo. The relevance of these results to elucidation of the
role of IL-6 in plasma cell tumorigenesis is discussed.
Volume 80,
Issue 1,
pp. 194-202,
07/01/1992
Copyright © 1992 by The American Society of Hematology
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