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: A. R. Zampronio, M. C. C. Melo, C. A. A. Silva, I. R. Pelá, S. J. Hopkins, G. E. P. Souza
Format: Article
Language:English
Published: Wiley 1994-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/S0962935194000517
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author A. R. Zampronio
M. C. C. Melo
C. A. A. Silva
I. R. Pelá
S. J. Hopkins
G. E. P. Souza
author_facet A. R. Zampronio
M. C. C. Melo
C. A. A. Silva
I. R. Pelá
S. J. Hopkins
G. E. P. Souza
author_sort A. R. Zampronio
collection DOAJ
description 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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spelling doaj-art-1f54607117fb4929a2a476f73a6ccb8e2025-08-20T02:04:20ZengWileyMediators of Inflammation0962-93511466-18611994-01-013536537310.1155/S0962935194000517A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated MacrophagesA. R. Zampronio0M. C. C. Melo1C. A. A. Silva2I. R. Pelá3S. J. Hopkins4G. E. P. Souza5Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, S.P. 14049-903, BrazilLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, S.P. 14049-903, BrazilLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, S.P. 14049-903, BrazilLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, S.P. 14049-903, BrazilUniversity of Manchester, Rheumatic Diseases Centre, Hope Hospital, Salford M6 8HD, UKLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, S.P. 14049-903, BrazilThe 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.http://dx.doi.org/10.1155/S0962935194000517
spellingShingle A. R. Zampronio
M. C. C. Melo
C. A. A. Silva
I. R. Pelá
S. J. Hopkins
G. E. P. Souza
A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
Mediators of Inflammation
title A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
title_full A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
title_fullStr A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
title_full_unstemmed A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
title_short A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages
title_sort pre formed pyrogenic factor released by lipopolysaccharide stimulated macrophages
url http://dx.doi.org/10.1155/S0962935194000517
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