title: Long-term amphetamine treatment exacerbates inflammatory lung reaction while decreases airway hyper-responsiveness after allergic stimulus in rats.
abstract: Asthma is an allergic lung disease can be modulated by drugs that modify the activity of central nervous system (CNS) such as amphetamine (AMPH). AMPH is a highly abused drug that exerts potent effects on behavior and immunity. In this study we investigated the mechanism involved in the effects of long-term AMPH treatment on the increased magnitude of allergic lung response. We evaluated mast cells degranulation, cytokines release, airways responsiveness and, expression of adhesion molecules. Male Wistar rats were treated with AMPH or vehicle (PBS) for 21 days and sensitized with ovalbumin (OVA) one week after the first injection of vehicle or AMPH. Fourteen days after the sensitization, the rats were challenged with an OVA aerosol, and 24h later their parameters were analyzed. In allergic rats, the treatment with AMPH exacerbated the lung cell recruitment due increased expression of ICAM-1, PECAM-1 and Mac-1 in granulocytes and macrophages recovered from bronchoalveolar lavage. Elevated levels of IL-4, but decreased levels of IL-10 were also found in samples of lung explants after AMPH treatment. Conversely, the ex-vivo tracheal hyper-responsiveness to methacholine (MCh) was reduced by AMPH treatment, whereas the force contraction of tracheal segments due to in vitro antigen challenge remained unaltered. Our findings suggest that lung inflammation and airway hyper-responsiveness due to OVA challenge are under the distinct control of AMPH during long-term treatment. Our data strongly indicate that AMPH positively modulates allergic lung inflammation via the increase of ICAM-1, PECAM-1, Mac-1 and IL-4. AMPH also abrogates the release of the anti-inflammatory cytokine IL-10.
authors.affiliation: Post Graduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University, São Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro de Oliveira
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-dos-Santos-Franco
authors.forename: Beatriz Golegã
authors.initials: BG
authors.lastname: Acceturi
authors.forename: Eduardo Kenji
authors.initials: EK
authors.lastname: Hamasato
authors.forename: Isabel Daufenback
authors.initials: ID
authors.lastname: Machado
authors.forename: João Antônio
authors.initials: JA
authors.lastname: Gimenes Júnior
authors.forename: Rodolfo de Paula
authors.initials: RP
authors.lastname: Vieira
authors.forename: Amílcar Sabino
authors.initials: AS
authors.lastname: Damazo
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares-de-Lima
authors.forename: João
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D016207:Cytokines; D013566:Sympathomimetics; D010047:Ovalbumin; D000661:Amphetamine