COMPARISON OF THE PULMONARY DISTRIBUTION AND EFFICACY OF ANTIBODIES GIVEN TO MICE BY INTRATRACHEAL INSTILLATION OR AEROSOL INHALATION

The respiratory tract is the portal of entry and target organ of many aerosolized toxins and infective agents, and there is increasing need for testing the efficacy of potential therapeutic agents delivered dir ectly into the lungs, Intratracheal instillation and aerosol inhalatio n are the two methods most often used to introduce drugs, toxins, or i nfective agents into the respiratory tract of experimental animals, In this study we compared the distribution and efficacy of antibodies gi ven to mice by aerosol inhalation or intratracheal instillation. We de termined the pulmonary distribution of these antibodies by immunohisto chemistry and observed the distribution and severity of pulmonary lesi ons that developed after exposure to aerosolized ricin, Although antib odies administered by either method prevented death, we found that ins tilled antibodies tended to concentrate around terminal airways and of ten failed to reach peripheral lung fields. Sometimes entire lung lobe s were missed by the instillation route, Acute and chronic pulmonary l esions developed in the unprotected areas of instillation-treated lung s, in contrast, aerosolized antibodies covered all pulmonary surfaces and effectively prevented ricin-induced lesions throughout the lungs, Our findings suggest that the aerosol inhalation method may be prefera ble for evaluating the efficacy of therapeutic agents in the respirato ry tract because of the failure of instilled agents to reach and prote ct peripheral alveoli.