Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.

BACKGROUND: The model of pleurisy induced by carrageenan exhibits a biphasic response (4 and 48 h) and permits the quantification of exudate, cell migration and certain enzymes such as myeloperoxidase (MPO) and adenosine-deaminase (ADA) that are markers of activated leukocytes. AIMS: The present stu...

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Main Authors: Dalmarco, Eduardo Monguilhott, Fröde, Tânia Silvia, Medeiros, Yara Santos
Format: Online
Language:English
Published: 2002
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781680/
id pubmed-1781680
recordtype oai_dc
spelling pubmed-17816802007-01-25 Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy. Dalmarco, Eduardo Monguilhott Fröde, Tânia Silvia Medeiros, Yara Santos Research Article BACKGROUND: The model of pleurisy induced by carrageenan exhibits a biphasic response (4 and 48 h) and permits the quantification of exudate, cell migration and certain enzymes such as myeloperoxidase (MPO) and adenosine-deaminase (ADA) that are markers of activated leukocytes. AIMS: The present study evaluates whether there exists, in the pleurisy model, a significant inhibition of ADA and MPO enzymes, leukocyte kinetics and other markers of inflammation [nitric oxide (NO) levels, exudation] caused by methotrexate treatment by the intraperitoneal (i.p.) route. METHODS: The pleurisy was induced by carrageenan (1%) in mice, and the parameters were analyzed 4 and 48 h after. RESULTS: After the induction of inflammation (4 h), methotrexate (20 mg/kg, i.p., 24 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), NO levels and MPO activity (p < 0.01), but not ADA activity and fluid leakage (p > 0.05). Regarding the second phase of pleurisy (48 h), methotrexate (40 mg/kg, i.p., 0.5 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), fluid leakage, NO levels (p < 0.01), and ADA and MPO activity (p < 0.05). CONCLUSIONS: These findings support the evidence that the acute administration of methotrexate has an important systemic anti-inflammatory activity in the studied inflammatory model. This effect was due to a significant inhibition on both neutrophil and mononuclear cells, being less marked in relation to exudation 48 h after. In relation to the enzymes studied and to NO levels, the findings support the evidence that methotrexate inhibits both enzymes (MPO and ADA) from leukocytes at the site of injury, thus reflecting the activation of both neutrophils and lymphocytes, respectively. Furthermore, the inhibiting effect on NO in both phases of pleurisy induced by carrageenan (4 and 48 h) indicates that methotrexate acts on constitutive and/or inducible NO synthases by means of different cells of the pleural cavity. 2002-10 /pmc/articles/PMC1781680/ /pubmed/12467522 http://dx.doi.org/10.1080/09629350210000015700 Text en
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
spellingShingle Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
author_facet Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
author_sort Dalmarco, Eduardo Monguilhott
title Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title_short Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title_full Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title_fullStr Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title_full_unstemmed Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title_sort effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
description BACKGROUND: The model of pleurisy induced by carrageenan exhibits a biphasic response (4 and 48 h) and permits the quantification of exudate, cell migration and certain enzymes such as myeloperoxidase (MPO) and adenosine-deaminase (ADA) that are markers of activated leukocytes. AIMS: The present study evaluates whether there exists, in the pleurisy model, a significant inhibition of ADA and MPO enzymes, leukocyte kinetics and other markers of inflammation [nitric oxide (NO) levels, exudation] caused by methotrexate treatment by the intraperitoneal (i.p.) route. METHODS: The pleurisy was induced by carrageenan (1%) in mice, and the parameters were analyzed 4 and 48 h after. RESULTS: After the induction of inflammation (4 h), methotrexate (20 mg/kg, i.p., 24 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), NO levels and MPO activity (p < 0.01), but not ADA activity and fluid leakage (p > 0.05). Regarding the second phase of pleurisy (48 h), methotrexate (40 mg/kg, i.p., 0.5 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), fluid leakage, NO levels (p < 0.01), and ADA and MPO activity (p < 0.05). CONCLUSIONS: These findings support the evidence that the acute administration of methotrexate has an important systemic anti-inflammatory activity in the studied inflammatory model. This effect was due to a significant inhibition on both neutrophil and mononuclear cells, being less marked in relation to exudation 48 h after. In relation to the enzymes studied and to NO levels, the findings support the evidence that methotrexate inhibits both enzymes (MPO and ADA) from leukocytes at the site of injury, thus reflecting the activation of both neutrophils and lymphocytes, respectively. Furthermore, the inhibiting effect on NO in both phases of pleurisy induced by carrageenan (4 and 48 h) indicates that methotrexate acts on constitutive and/or inducible NO synthases by means of different cells of the pleural cavity.
publishDate 2002
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781680/
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