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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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Autores principales: Dalmarco, Eduardo Monguilhott, Fröde, Tânia Silvia, Medeiros, Yara Santos
Formato: Texto
Lenguaje:English
Publicado: 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781680/
https://www.ncbi.nlm.nih.gov/pubmed/12467522
http://dx.doi.org/10.1080/09629350210000015700
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author Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
author_facet Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
author_sort Dalmarco, Eduardo Monguilhott
collection PubMed
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.
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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 Mediators Inflamm 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
spellingShingle Research Article
Dalmarco, Eduardo Monguilhott
Fröde, Tânia Silvia
Medeiros, Yara Santos
Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
title 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_short 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.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781680/
https://www.ncbi.nlm.nih.gov/pubmed/12467522
http://dx.doi.org/10.1080/09629350210000015700
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