59. Long-term amphetamine treatment increases inflammatory lung reaction and reduces upper airway reactivity after allergic lung inflammation in rats

Abstract

The purpose of this study was to investigate the repercussions of long-term AMPH treatment on the magnitude of allergic lung inflammation. Male Wistar rats were treated with AMPH or vehicle (PBS) during 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 OVA by aerosol and, 24 h later the parameters were analyzed. In rats treated with AMPH, the OVA challenge exacerbated the increased cell recruitment into the lung and the cellular expression of ICAM-1, PECAM-1 and Mac-1 of cells recovered in bronchoalveolar lavage. Similarly, elevated levels of IL-4 but decreased levels of IL-10 were also found in samples of lung explants from allergic rats after AMPH treatment. Conversely, the ex-vivo tracheal reactivity to methacholine (MCh) was reduced by AMPH treatment, whereas the force contraction of tracheal segments due to in vitro antigen challenge did not alter. Our findings suggest that lung inflammation and upper airway reactivity due to OVA-challenge are under distinct control of AMPH long-term treatment. Our data strongly indicate that AMPH modulates positively the allergic lung inflammation by mechanisms involving the increase of ICAM-1, PECAM-1, Mac-1 and IL-4 and abrogates the release of anti-inflammatory cytokine IL-10.