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Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy.
Transpl Immunol. 2006 Aug; 16(2):105-11.TI

Abstract

INTRODUCTION

Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis.

OBJECTIVES

This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone.

MATERIALS AND METHODS

Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 micromol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFalpha and Il-1beta), nitrite/nitrate (NOx), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols.

RESULTS

In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation (P < 0.01). Under the same conditions, Tacrolimus and dexamethasone did not modify the blood's white or red cells (P > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P < 0.01), whereas the inhibition of exudation was less marked (up to 2 h) (P < 0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1beta and TNFalpha levels (P < 0.01), but only Tacrolimus inhibited ADA activity (P < 0.01). On the other hand, dexamethasone, but not Tacrolimus, inhibited NOx levels (P < 0.01). In the same conditions, Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P (P < 0.05). In a similar manner, dexamethasone inhibited leukocyte influx induced by bradykinin and histamine (P < 0.05). Regarding exudation effects, dexamethasone markedly inhibited this parameter induced by BK, HIS or SP, whereas Tacrolimus only inhibited exudation caused by HIS (P < 0.05).

CONCLUSIONS

The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFalpha, IL-1beta), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus's actions.

Authors+Show Affiliations

Department of Medical Science, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-970, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16860713

Citation

Pereira, Robson, et al. "Antiinflammatory Effects of Tacrolimus in a Mouse Model of Pleurisy." Transplant Immunology, vol. 16, no. 2, 2006, pp. 105-11.
Pereira R, Medeiros YS, Fröde TS. Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy. Transpl Immunol. 2006;16(2):105-11.
Pereira, R., Medeiros, Y. S., & Fröde, T. S. (2006). Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy. Transplant Immunology, 16(2), 105-11.
Pereira R, Medeiros YS, Fröde TS. Antiinflammatory Effects of Tacrolimus in a Mouse Model of Pleurisy. Transpl Immunol. 2006;16(2):105-11. PubMed PMID: 16860713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy. AU - Pereira,Robson, AU - Medeiros,Yara Santos, AU - Fröde,Tânia Silvia, Y1 - 2006/05/30/ PY - 2006/01/17/received PY - 2006/04/18/revised PY - 2006/04/25/accepted PY - 2006/7/25/pubmed PY - 2006/9/16/medline PY - 2006/7/25/entrez SP - 105 EP - 11 JF - Transplant immunology JO - Transpl. Immunol. VL - 16 IS - 2 N2 - INTRODUCTION: Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis. OBJECTIVES: This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone. MATERIALS AND METHODS: Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 micromol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFalpha and Il-1beta), nitrite/nitrate (NOx), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols. RESULTS: In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation (P < 0.01). Under the same conditions, Tacrolimus and dexamethasone did not modify the blood's white or red cells (P > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P < 0.01), whereas the inhibition of exudation was less marked (up to 2 h) (P < 0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1beta and TNFalpha levels (P < 0.01), but only Tacrolimus inhibited ADA activity (P < 0.01). On the other hand, dexamethasone, but not Tacrolimus, inhibited NOx levels (P < 0.01). In the same conditions, Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P (P < 0.05). In a similar manner, dexamethasone inhibited leukocyte influx induced by bradykinin and histamine (P < 0.05). Regarding exudation effects, dexamethasone markedly inhibited this parameter induced by BK, HIS or SP, whereas Tacrolimus only inhibited exudation caused by HIS (P < 0.05). CONCLUSIONS: The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFalpha, IL-1beta), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus's actions. SN - 0966-3274 UR - https://www.unboundmedicine.com/medline/citation/16860713/Antiinflammatory_effects_of_Tacrolimus_in_a_mouse_model_of_pleurisy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0966-3274(06)00069-4 DB - PRIME DP - Unbound Medicine ER -