A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
The aim of this study was to investigate the pyrogenic activity of factor(s) released by rat peritoneal macrophages following a brief stimulation with LPS. The effect of this factor on the number of circulating leukocytes and serum Fe, Cu and Zn levels, was also evaluated. The possibility that the c...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
1994-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S0962935194000517 |
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| Summary: | The aim of this study was to investigate the pyrogenic activity of
factor(s) released by rat peritoneal macrophages following a brief
stimulation with LPS. The effect of this factor on the number of
circulating leukocytes and serum Fe, Cu and Zn levels, was also
evaluated. The possibility that the content of interleukin
(IL)-1β, IL-6 and tumour necrosis factor (TNF) in the
supernatant could explain the observations was investigated.
Supernatant produced over a period of 1 h by peritoneal macrophages,
following a 30 min incubation with LPS at 37°C, was
ultrafiltered through a 10 000 MW cut-off Amicon membrane,
sterilized, and concentrated 2.5, 5, 10 and 20 times. The
intravenous (i.v.) injection of this supernatant induced a
concentration-dependent fever in rats with a maximal response at 2
h. The pyrogenic activity was produced by macrophages elicited with
thioglycollate and by resident cells. The supernatants also induced
neutrophilia and reduction in Fe and Zn 6 h after the injection.
Absence of activity in boiled supernatants, or supernatants from
macrophages incubated at 4°C with LPS, indicates that LPS was
not responsible for the activity. In vitro treatment
with indomethacin (Indo), dexamethasone (Dex), or cycloheximide
(Chx) did not modify the release of pyrogenic activity into the
supernatant or its effects on the reduction in serum metal levels.
Although Chx abolished the production of mediator(s) inducing
neutrophilia, and Dex reduced the induction of IL-1β, TNF and
IL-6, injection of the highest concentration of these cytokines
detected in the supernatants did not induce fever. In
vivo treatment with Dex, but not Indo, abolished the fever
induced by the supernatant. These results suggest that macrophages
contain pre-formed pyrogenic mediator(s), not related to IL-1β,
IL-6 or TNF, that acts indirectly and independently of
prostaglandtn. It also seems likely that the pyrogenic activity is
related to the factor responsible for the reduction of serum Fe and
Zn levels, but not the neutrophilia. |
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| ISSN: | 0962-9351 1466-1861 |