966 AN ANIMAL MODEL OF LATE PULMONARY RESPONSES TO ANTIGEN CHALLENGE: EFFECTS OF TRANSFUSION WITH “BLOCKING” ANTISERA AND BRONCHODILATOR ADMINISTRATION

Abstract

Late pulmonary responses (LPR) to mold antigens are a major cause of morbidity in asthmatic patients. We have developed a rabbit model of IgE-dependent LPR to Alternaria aerosol challenge. Rabbits with both IgG and IgE antibodies against Alternaria had blunted LPR measured by increases in total pulmonary resistence (RL) and decreases in dynamic compliance (Cdyn) compared with IgE-only rabbits. To note if passive transfer of IgG would diminish LPR, rabbits were transfused with 30 ml of antiserum heated to remove IgE activity. Marked early pulmonary responses (EPR) (RL=135% of baseline, Cdyn=64%) and LPR (RL 151%, Cdyn=48%) were blunted in three out of four rabbits after transfusion (RL=115%, Cdyn=100% for EPR, RL=119%, Cdyn=100% for LPR). The fourth rabbit had a larger EPR before transfusion compared with the other three (RL=150%, Cdyn =38%), which was partially diminished after (RL=133%, Cdyn=38%). No consistent changes in WBC, differential, platelet count or hemolytic complement were noted in 3 rabbits. Intravenous isoproterenol 6 hrs after challenge did not reverse the LPR. Thus LPR in human asthma as well as in this model is poorly responsive to bronchodilators. Our results suggest that abbrogation of the early, anaphylactic response (e.g. through generation of “blocking” antibody) is important in suppression of the LPR in Alternaria sensitivity. Peripheral leukocyte and complement changes may not be important in the LPR.