Effects of amphetamine on immune-mediated lung inflammatory response in rats.
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.


CONCLUSIONS
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.
Ligeiro-Oliveira
A P
AP
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Fialho de Araújo
A M
AM
Lazzarini
R
R
Silva
Z L
ZL
De Nucci
G
G
Muscará
M N
MN
Tavares de Lima
W
W
Palermo-Neto
J
J
D000661:Amphetamine / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D003345:Corticosterone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D038042:Myelopoiesis / Q000187:drug effects* / Q000276:immunology; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000276:immunology; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D010047:Ovalbumin; D000661:Amphetamine; D003345:Corticosterone; D008797:Metyrapone