Pharmacological modulation of eosinophil influx into the lungs of Brown Norway rats.
A model of lung inflammation was developed in Brown Norway rats. Intense lung eosinophilia was induced by a single intravenous injection of Sephadex G-200 particles. The eosinophilia observed was preceded by an increase in cysteinyl leukotrienes found in lung lavage fluids. Theophylline and albuterol were tested in the model and found to be inactive, while dexamethasone was effective. Zileuton, a specific leukotriene inhibitor, was found to effectively inhibit leukotriene formation and the influx of eosinophils into the lungs of these Sephadex-treated animals. Studies with specific leukotriene D4 antagonists of the cysLT1 type receptor indicate that this leukotriene receptor is probably not involved directly in the eosinophilic inflammation. This model appears to be useful in characterizing potential anti-inflammatory effects of inhibitors by evaluating their ability to prevent eosinophil influx into the lung.
Namovic
M T
MT
AP9 Immunosciences Research Area, Department 47 K, Abbott Laboratories, Abbott Park, IL 60064, USA.
Walsh
R E
RE
Goodfellow
C
C
Harris
R R
RR
Carter
G W
GW
Bell
R L
RL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology*; D003911:Dextrans; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007476:Ionophores / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D013806:Theophylline / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; D007476:Ionophores; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D017997:Leukotriene C4; D000001:Calcimycin; C025614:sephadex; D013806:Theophylline; C063449:zileuton; D006918:Hydroxyurea