Amphetamine modulates cellular recruitment and airway reactivity in a rat model of allergic lung inflammation

Autor(es)

Ligeiro de Oliveira, Ana Paula ^[1] ; Lino-dos-Santos-Franco, Adriana ^[1] ; Hamasato, Eduardo Kenji ^[2] ; Quinteiro-Filho, Wanderley ^[2] ; Hebeda, Cristina Bichels ^[3] ; Damazo, Amilcar Sabino ^[4] ; Poliselli Farsky, Sandra Helena ^[3] ; Tavares-de-Lima, Wothan ^[1] ; Palermo-Neto, Joao ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Vet Med, Lab Appl Pharmacol & Toxicol, BR-05508900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil

^[4] Fed Univ Cuiaba, Dept Basic Sci Hlth, Fac Med Sci, Cuiaba, Mato Grosso - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicology Letters; v. 200, n. 1-2, p. 117-123, JAN 15 2011.
• Citações Web of Science: 14

Resumo

Asthma is characterized by pulmonary cellular infiltration, vascular exudation and airway hyperresponsiveness. Several drugs that modify central nervous system (CNS) activity can modulate the course of asthma. Amphetamine (AMPH) is a highly abused drug that presents potent stimulating effects on the CNS and has been shown to induce behavioral, biochemical and immunological effects. The purpose of this study was to investigate the effects of AMPH on pulmonary cellular influx, vascular permeability and airway reactivity. AMPH effects on adhesion molecule expression, IL-10 and IL-4 release and mast cell degranulation were also studied. Male Wistar rats were sensitized with ovalbumin (OVA) plus alum via subcutaneous injection. One week later, the rats received another injection of OVA-alum (booster). Two weeks after this booster, the rats were subjected to AMPH treatment 12 h prior to the OVA airway challenge. In rats treated with AMPH, the OVA challenge reduced cell recruitment into the lung, the vascular permeability and the cellular expression of ICAM-1 and Mac-1. Additionally, elevated levels of IL-10 and IL-4 were found in samples of lung explants from allergic rats. AMPH treatment, in comparison, increased IL-10 levels but reduced those of IL-4 in the lung explants. Moreover, the tracheal responsiveness to methacholine (MCh), as well as to an in vitro OVA challenge, was reduced by AMPH treatment, and levels of PCA titers were not modified by the drug. Our findings suggest that single AMPH treatment down-regulates several parameters of lung inflammation, such as cellular migration, vascular permeability and tracheal responsiveness. These results also indicate that AMPH actions on allergic lung inflammation include endothelium-leukocyte interaction mechanisms, cytokine release and mast cell degranulation. (C) 2010 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 08/50766-1 - Repercussao pulmonar e sistemica apos exposicao de ratos ao formaldeido: papel regulador das especies reativas derivadas do oxigenio e do nitrogenio.
• Beneficiário: Adriana Lino dos Santos Franco
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/07208-0 - Modulação da inflamação pulmonar alérgica por adjuvantes ou tolerância imunológica
• Beneficiário: Momtchilo Russo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/55631-4 - Estudo da participação dos hormônios sexuais femininos na asma experimental induzida em linhagens de camundongos geneticamente selecionados (AIRmax e AIRmin)
• Beneficiário: Wothan Tavares de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular