Modification of acute and late-phase allergic responses to ovalbumin with lipopolysaccharide.
BACKGROUND
We have previously shown that lipopolysaccharide (LPS) exposure in sensitised animals 18 h after ovalbumin (OVA) challenge inhibits OVA-induced airway hyper-responsiveness (AHR). In the present study, we investigated the effect of LPS on OVA-induced acute and late-phase allergic responses in sensitised rats when challenged with OVA.


METHODS
Rats were sensitised with OVA and 11 days later challenged with 1% OVA in the presence or absence of LPS (0.5-50 microg/ml) given in the same nebulizer. Acute responses to OVA were measured each minute for 30 min after challenge. In a separate group of animals, late-phase responses to OVA were determined at 24 h. At the end of each study, Evans blue dye was injected and animals sacrificed 30 min later. Bronchoalveolar lavage was obtained to monitor inflammatory cell migration and microvascular leakage.


RESULTS
OVA challenge in sensitised animals produced an acute response with changes in lung mechanics peaking 10.0 +/- 0.9 min after OVA and returning to baseline within 30 min. This was followed 24 h later by increased responses to methacholine chloride (MCh), inflammatory cell influx and increased Evans blue leakage into the lungs. Presence of 5 or 50 microg/ml LPS in the nebulizer during OVA challenge altered the kinetics of the acute-phase response, with an immediate decrease in lung function (time to peak decreased from 10.3 +/- 1.2 to 1.8 +/- 0.2 and 2.2 +/- 0.3 min, respectively: p < 0.001, n = 6) and a dose-dependent attenuation of late-phase AHR, cellular influx (n = 5, p < 0.001) and Evans blue leakage (n = 5, p < 0.001) at 24 h.


CONCLUSIONS
In summary, co-administration of OVA with LPS modifies both the acute and late-phase responses to the allergen, inducing an earlier acute change in lung function and a dose-dependent inhibition of late-phase responses to the allergen.
Tulic
Mark K
MK
Division of Clinical Sciences, TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia. meri.tulic@mcgill.ca
Holt
Patrick G
PG
Sly
Peter D
PD
D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004396:Coloring Agents / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005070:Evans Blue / Q000737:chemistry; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000276:immunology*; D051381:Rats; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric
D004396:Coloring Agents; D008070:Lipopolysaccharides; D007073:Immunoglobulin E; D005070:Evans Blue; D010047:Ovalbumin