The effect of R 15.7/HO, an anti‐CD18 antibody, on the late airway response and airway hyperresponsiveness in an allergic rabbit model

The effects of a mouse (IgG1 fraction) anti‐CD 18 neutralizing antibody (R15.7) on allergen‐induced late airway response (LAR), airway hyperresponsiveness (AHR) and cellular recruitment were investigated in an allergic rabbit model. Litter‐matched NZW rabbits immunized within 24 h of birth with Alte...

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Veröffentlicht in:British journal of pharmacology 1997-06, Vol.121 (4), p.671-678
Hauptverfasser: El‐Hashim, A. Z., Jacques, C. A., Herd, C. M., Lee, T. H., Page, C. P.
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Sprache:eng
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Zusammenfassung:The effects of a mouse (IgG1 fraction) anti‐CD 18 neutralizing antibody (R15.7) on allergen‐induced late airway response (LAR), airway hyperresponsiveness (AHR) and cellular recruitment were investigated in an allergic rabbit model. Litter‐matched NZW rabbits immunized within 24 h of birth with Alternaria tenuis (i.p.) and subsequently exposed to the allergen (i.p.) for the first 3 months of life were challenged with inhaled allergen as adult rabbits. Lung function in terms of dynamic compliance (Cdyn; ml cmH2O−1) and total lung resistance (RL; cmH2O−1 s−1) was monitored for 6 h following the allergen challenge. On day 16, separate groups of rabbits were pretreated with either control antibody (a non‐binding mouse IgG1, 1 mg kg−1, i.v.) or R15.7 (1 mg kg−1, i.v.) and 1 h later all were challenged with Alternaria tenuis and lung function monitored thereafter. Airway responsiveness to inhaled histamine was assessed by measuring RL and Cdyn 24 h before and after allergen challenge and bronchoalveolar lavage (BAL) was also performed 24 h before and after allergen challenge. Pretreatment of rabbits with the control antibody had no effect on the LAR as measured by AUC (Cdyn, 0–6 h). However, the magnitude of the LAR following treatment with R15.7 was significantly reduced when compared to LAR demonstrated on 1st challenge (P
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0701176