ABSTRACT
OBJECTIVE: The present study analyzed the effects of acute amphetamine (AMPH) treatment on immune-mediated lung inflammatory response in rats. METHODS: There were four experiments. In the first and second experiments, rats were treated with AMPH (1 mg/kg) or 0.9% NaCl, and locomotor activity (experiment 1) and serum AMPH concentrations (experiment 2) were measured 1 or 12 h after treatment. In the third experiment, rats which were immunized with ovalbumin (OVA) were treated 14 days later with 0.9% NaCl or AMPH (1 mg/kg). Twelve hours after these treatments, all animals were submitted to challenge by 1% OVA inhalation being analyzed afterwards for bronchoalveolar lavage fluid (BAL), peripheral blood and bone marrow cellularity. In the fourth and final experiment, rats were treated and studied as for experiment 3, except that half of the animals within each group were previously treated with metyrapone prior to the OVA challenge. RESULTS: In the non-immunized rats, AMPH treatment induced an increase in locomotor activity synchronized to high serum AMPH concentrations 1 h after, but not 12 h after treatment. In OVA-challenged rats, AMPH treatment decreased the total number of inflammatory cells, recovered in both BAL and peripheral blood and increased the total number of bone marrow cells. These effects, observed 1 day after OVA challenge, were abrogated by previous metyrapone treatment. CONCLUSION: AMPH treatment changed HPA-axis responsiveness to the stress condition imposed by the OVA challenge decreasing lung and blood leukocytes cellularity most probably via corticosterone actions on bone marrow activity.
Subject(s)
Amphetamine/pharmacology , Chemotaxis, Leukocyte/drug effects , Hypothalamo-Hypophyseal System/drug effects , Myelopoiesis/drug effects , Neuroimmunomodulation/drug effects , Pneumonia/immunology , Amphetamine/blood , Animals , Bone Marrow/drug effects , Bone Marrow/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Chemotaxis, Leukocyte/immunology , Corticosterone/metabolism , Down-Regulation/drug effects , Down-Regulation/immunology , Enzyme Inhibitors/pharmacology , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/metabolism , Inflammation Mediators/pharmacology , Leukocyte Count , Leukocytes/cytology , Leukocytes/drug effects , Leukocytes/immunology , Male , Metyrapone/pharmacology , Motor Activity/drug effects , Motor Activity/physiology , Myelopoiesis/immunology , Neuroimmunomodulation/immunology , Ovalbumin/pharmacology , Pneumonia/chemically induced , Pneumonia/physiopathology , Rats , Rats, WistarABSTRACT
Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.
