Montelukast, Leukotriene Inhibitor, Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation

Autor(es):Mostrar menos -

Davino-Chiovatto, Jaime Eduardo ^[1] ; Oliveira-Junior, Manoel Carneiro ^[2] ; MacKenzie, BreAnne ^[2] ; Santos-Dias, Alana ^[2] ; Almeida-Oliveira, Ana Roberta ^[2] ; Jonco Aquino-Junior, Jefferson Comin ^[2] ; Brito, Aurileia Aparecida ^[1] ; Rigonato-Oliveira, Nicole Cristine ^[1] ; Damaceno-Rodrigues, Nilsa Regina ^[3] ; Ligeiro Oliveira, Ana Paula ^[1] ; Silva, Alessandro Pereira ^[4] ; Consolim-Colombo, Fernanda Marciano ^[1] ; Aimbire, Flavio ^[5] ; Castro-Faria-Neto, Hugo Caire ^[6] ; Vieira, Rodolfo Paula ^{[2, 7, 8, 9]}

Afiliação do(s) autor(es)

^[1] Nove de Julho Univ UNINOVE, Sao Paulo, SP - Brazil

^[2] Brazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Pathol LIM 59, Sao Paulo, SP - Brazil

^[4] Univ Mogi das Cruzes, Postgrad Program Biomed Engn, Mogi Das Cruzes, SP - Brazil

^[5] Fed Univ Sao Paulo UNIFESP, Sao Jose Dos Campos, SP - Brazil

^[6] Osvaldo Cruz Fdn, Osvaldo Cruz Inst IOC, Lab Immunopharmacol, Rio De Janeiro, RJ - Brazil

^[7] Fed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP - Brazil

^[8] Univ Brasil, Postgrad Program Bioengn & Biomed Engn, Sao Paulo, SP - Brazil

^[9] Anhembi Morumbi Univ, Sch Med, Ave Deputado Benedito Matarazzo 4050, Sao Jose Dos Campos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVOS DE BRONCONEUMOLOGIA; v. 55, n. 11, p. 573-580, NOV 2019.
• Citações Web of Science: 1

Resumo

Objectives: Some pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant, a cell centrally involved in acute respiratory distress syndrome (ARDS); a syndrome lacking effective treatment. Considering the beneficial effects of the leukotriene receptor inhibitor, montelukast, on other lung diseases, whether montelukast attenuates inflammation in a mouse model of ARDS, and whether it reduces LPS stimulated activation of human neutrophils was investigated. Methods: Thirty-five C57Bl/6 mice were distributed into control (PBS) + 24h, LPS + 24 h (10 mu g/mouse), control +48 h, LPS +48 h, and LPS 48 h + Montelukast (10 mg/kg). In addition, human neutrophils were incubated with LPS (1 mu g/mL) and treated with montelukast (10 mu M). Results: Oral-tracheal administration of montelukast significantly attenuated total cells (P < .05), macrophages (P< .05), neutrophils (P< .01), lymphocytes (P< .001) and total protein levels in BAL (P < .05), as well as IL-6 (P < .05), CXCL1/KC (P < .05), IL-17 (P< .05) and TNF-alpha (P< .05). Furthermore, montelukast reduced neutrophils (P<.001), lymphocytes (P < .01) and macrophages (P< .01) in the lung parenchyma. In addition, montelukast restored BAL VEGF levels (P<.05). LTB4 receptor expression (P< .001) as well as NF-kappa B (P<.001), a downstream target of LPS, were also reduced in lung parenchymal leukocytes. Furthermore, montelukast reduced IL-8 (P < .001) production by LPS-treated human neutrophils. Conclusion: In conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils. (C) 2019 SEPAR. Published by Elsevier Espatia, S.L.U. All rights reserved. (AU)

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