Modulation of citric acid-induced cough following lipopolysaccharide-mediated neutrophilia in the guinea pig.
This investigation examined a possible correlation between lipopolysaccharide (LPS)-induced pulmonary neutrophilia and cough. Conscious male guinea pigs were acutely exposed to aerosolized LPS and thereafter at various times challenged with citric acid aerosol (CA; 250mM) to induce cough followed by bronchoalveolar lavage (BAL) to quantitate inflammatory cell accumulation. LPS caused a hyporesponsive cough at 24h post-LPS with neutrophilia apparent from 2h post-LPS. By 96h post-LPS both cough and neutrophilia had returned towards normal. Dexamethasone (DEX, 2mgkg(-1)/day for 3 days prior) did not affect the cough hyporesponsiveness at 24h; however it attenuated LPS-induced BAL fluid neutrophilia. Since LPS can stimulate inducible nitric oxide synthase (iNOS) we hypothesized that the cough hyporesponsiveness may involve nitric oxide. To investigate this we treated animals with an aerosolized iNOS inhibitor 1400W (1mM) immediately prior to LPS. 1400W had no significant effect on either cough hyporesponsiveness or BAL fluid neutrophilia at 24h post-LPS. Despite differing effects on neutrophilia, these findings clearly indicate that neither DEX nor iNOS inhibition had any direct effect on LPS-induced cough hyporesponsiveness. The mechanism underlying the LPS-induced cough hyporesponsiveness does not appear to be directly linked to LPS-induced neutrophilic inflammation.
Brown
Claire
C
UCB Research Inc., UCB Pharma, 840 Memorial Dr., Cambridge, MA 02139, USA. claire.brown@genzyme.com
Selig
William M
WM
Ellis
James L
JL
D000280:Administration, Inhalation; D000336:Aerosols; D000578:Amidines / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001596:Benzylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019343:Citric Acid / Q000008:administration & dosage / Q000633:toxicity; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D009330:Nebulizers and Vaporizers; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000336:Aerosols; D000578:Amidines; D000893:Anti-Inflammatory Agents; D001596:Benzylamines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019343:Citric Acid; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II