Effect of heparin on antigen‐induced airway responses and pulmonary leukocyte accumulation in neonatally immunized rabbits

The effect of single administrations of aerosolized heparin, low molecular weight heparin (LMWH) and the linear polyanionic molecule, polyglutamic acid (PGA) were examined on antigen‐induced airway hyperresponsiveness and leukocyte accumulation in neonatally immunized rabbits. Adult litter‐matched NZW rabbits immunized within 24 h of birth with Alternaria tenuis antigen were treated with heparin, LMWH or PGA prior to or following antigen challenge ( Alternaria tenuis ). For each drug‐treated group, a parallel group of rabbits were treated with the appropriate vehicle. In all groups, airway responsiveness to inhaled histamine and bronchoalveolar lavage (BAL) was performed 24 h prior to and following antigen challenge. Basal lung function in terms of resistance (R L ) and dynamic compliance (C dyn ) and acute bronchoconstriction was unaltered by pre‐treatment with heparin, LMWH or PGA compared to their respective vehicles 24 h prior to or following antigen challenge. In vehicle‐treated animals, airway hyperresponsiveness to inhaled histamine was indicated by an increase in the maximal responses of the cumulative concentration‐effect curves to histamine and reductions in R L PC 50 and C dyn PC 35 values 24 h following antigen challenge. Heparin and LMWH given prior to antigen challenge significantly inhibited the development of airway hyperresponsiveness, whereas PGA did not. When given following antigen challenge, all three drugs failed to inhibit the development of airway hyperresponsiveness. Eosinophil and neutrophil cell numbers in BAL fluid increased significantly 24 h following antigen challenge. Heparin, LMWH and PGA failed to inhibit the increase in cell numbers following antigen challenge whether given prior to or following antigen challenge.British Journal of Pharmacology (2000) 129 , 1585–1596; doi: 10.1038/sj.bjp.0703247