The effects of LY293111Na, a leukotriene B4 receptor antagonist, on the pulmonary neutrophilia and CD11b expression caused by inhalation of a leukotriene B4 aerosol in rhesus monkeys.
The dose-response relationship between aerosolized leukotriene B4 (LTB4 and pulmonary neutrohilia was examined in a group of five rhesus monkeys. The effects of an oral dose of LY293111Na on LTB4-aerosol-induced pulmonary neutrophilia were also examined. Ex vivo expression of CD11b receptors on polymorphonuclear leukocytes from bronchoalveolar lavage fluid and peripheral whole blood were also assessed. Up-regulation of CD11b adhesion receptors by LTB4 was assessed ex vivo on the peripheral whole blood. Pulmonary neutrophilia was linearly associated with dose of inhaled LTB4. LY293111Na, at 10 mg/kg, significantly blocked the profound bronchoalveolar lavage neutrophilia produced by LTB4 aerosol inhalation. A large (48%), but not statistically significant, reduction was seen for CD11b expression on bronchoalveolar lavage polymorphonuclear leukocytes after pretreatment with LY293111Na. LY293111Na did not significantly change the number of white blood cells in peripheral blood. LY293111Na did significantly attenuate the LTB4-induced up-regulation of CD11b receptors on peripheral blood neutrophils. We conclude that LY293111Na may be an effective oral treatment for diseases that involve neutrophilic inflammation.
Allen
D L
DL
Toxicology Research Laboratories, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana.
Hoffman
W P
WP
Marder
P
P
Matchett
M R
MR
Leiter
P A
PA
Abbott
D L
DL
Wolff
R K
RK
D000336:Aerosols; D000818:Animals; D001565:Benzoates / Q000097:blood / Q000494:pharmacology*; D005434:Flow Cytometry; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008253:Macaca mulatta; D016177:Macrophage-1 Antigen / Q000032:analysis*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*
D000336:Aerosols; D001565:Benzoates; C094099:LY 293111; D016177:Macrophage-1 Antigen; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4