Effects of leukotriene B4 inhalation. Airway sensitization and lung granulocyte infiltration in the guinea pig.
Male Hartley guinea pigs were exposed by inhalation to leukotriene B4 (LTB4) and challenged 5 min or 4 h later with bronchoconstrictive aerosols of histamine or the divalent cationic ionophore A23187. Pulmonary gas trapping measured in excised lungs indicated the severity of post-challenge airway obstruction. Airway granulocyte infiltration was scored by an observer who was unaware of animal assignments. Treatment with LTB4 produced a marked influx of eosinophils and neutrophils into tracheal and bronchial airways. Granulocyte scores for LTB4-treated groups were 1.9 to 3.3 times higher than those for vehicle-treated groups at 5 min after exposure and 3.3 to 10.7 times higher at 4 h after exposure. Leukotriene B4 itself did not produce hyperinflation. However, histamine-induced gas trapping was increased 5 min after LTB4 exposure. Histamine responsiveness was unaffected 4 h after LTB4 treatment. In contrast, A23187-induced gas trapping was unaffected at 5 min, but diminished at 4 h after LTB4. Nonchemotactic stereoisomers of LTB4 did not produce granulocyte influx, but did produce altered airway responses similar to those seen for LTB4. We conclude that inhaled LTB4 produces airway granulocyte infiltration in the guinea pig and alterations in airway responsiveness that vary with the challenge stimulus and time after exposure. Alterations in airway responses may result from granulocyte-independent effects of LTB4 and its stereoisomers.
Silbaugh
S A
SA
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Stengel
P W
PW
Williams
G D
GD
Herron
D K
DK
Gallagher
P
P
Baker
S R
SR
D000336:Aerosols; D000402:Airway Obstruction / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007114:Immunization; D007975:Leukotriene B4 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D013997:Time Factors
D000336:Aerosols; D007975:Leukotriene B4; D000001:Calcimycin; D000431:Ethanol; D006632:Histamine; D004121:Dimethyl Sulfoxide