Chronic hypersensitivity pneumonitis produced in the rabbit by the adjuvant effect of inhaled muramyl dipeptide (MDP).

An established rabbit model of acute hypersensitivity pneumonitis was used to evaluate adjuvant properties of synthetic muramyl dipeptide (MDP), the minimal adjuvant-active structure of mycobacteria. The authors studied MDP as a substitute for mycobacteria in immunization and as adjuvant during repeated inhalation of antigen (ovalbumin). They found that MDP could substitute successfully for mycobacteria in sensitizing animals for acute alveolitis following subsequent inhalation of a combination of ovalbumin and MDP aerosol for 4 to 14 weeks resulted in the development of chronic granulomatous pneumonitis, characterized by alveolar wall thickening, granulomas, and infiltrations with lymphocytes and macrophages. In addition, MDP boosted systemic and local IgG and IgA antigen-specific antibodies. Inhaled MDP, itself neither antigenic nor mitogenic, acted therefore as adjuvant for continued immunologic inflammatory effector mechanisms in the rabbit lung, which are ordinarily suppressed when antigen alone is inhaled. Possible mechanisms include stimulation of effector T cells and macrophages or the failure of suppressive mechanisms, with or without participation of immune complexes. This is the first successful model of chronic granulomatous alveolitis produced by inhalation of soluble materials. Further exploration of adjuvant mechanisms in this system should help clarify the pathogenesis of immunologic lung diseases in man.