Epithelioid granuloma formation by a synthetic bacterial cell wall component, muramyl dipeptide (MDP).

A synthetic muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl-D-isoglutamine) is a minimal essential structure that is contained generally in bacterial cell walls and is responsible for their many biologic activities such as adjuvant activity, pyrogenicity, and a capacity to confer resistance against bacterial and viral infections. We found that this MDP evoked dose-dependently massive organized epithelioid granulomas in guinea pigs, when injected in the form of Freund-type water-in-oil emulsion. Granuloma formation reached a peak at 3 weeks. A minimal effective dose of MDP was 0.1 microgram. Essentially, no difference was observed qualitatively among granulomas evoked by MDP, MDP plus antigen, and killed tubercle bacilli incorporated in the emulsion. Quantitatively, however, MDP was stronger in its granulomagenic capacity than tubercle bacilli. Antigenicity of MDP was not detectable. These findings support our proposal that MDP may be a chemical structure in tubercle bacilli essential for epithelioid granuloma formation and that the MDP-induced epithelioid granuloma may be of a nonallergic nature.