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Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.
Mediators Inflamm. 2002 Oct; 11(5):299-306.MI

Abstract

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.

Authors+Show Affiliations

Department of Clinical Analysis, Center of Health Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-970, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12467522

Citation

Dalmarco, Eduardo Monguilhott, et al. "Effects of Methotrexate Upon Inflammatory Parameters Induced By Carrageenan in the Mouse Model of Pleurisy." Mediators of Inflammation, vol. 11, no. 5, 2002, pp. 299-306.
Dalmarco EM, Fröde TS, Medeiros YS. Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy. Mediators Inflamm. 2002;11(5):299-306.
Dalmarco, E. M., Fröde, T. S., & Medeiros, Y. S. (2002). Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy. Mediators of Inflammation, 11(5), 299-306.
Dalmarco EM, Fröde TS, Medeiros YS. Effects of Methotrexate Upon Inflammatory Parameters Induced By Carrageenan in the Mouse Model of Pleurisy. Mediators Inflamm. 2002;11(5):299-306. PubMed PMID: 12467522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy. AU - Dalmarco,Eduardo Monguilhott, AU - Fröde,Tânia Silvia, AU - Medeiros,Yara Santos, PY - 2002/12/7/pubmed PY - 2003/5/6/medline PY - 2002/12/7/entrez SP - 299 EP - 306 JF - Mediators of inflammation JO - Mediators Inflamm VL - 11 IS - 5 N2 - 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. SN - 0962-9351 UR - https://www.unboundmedicine.com/medline/citation/12467522/Effects_of_methotrexate_upon_inflammatory_parameters_induced_by_carrageenan_in_the_mouse_model_of_pleurisy_ L2 - https://doi.org/10.1080/09629350210000015700 DB - PRIME DP - Unbound Medicine ER -