Necrotic Inflammatory Reaction to Muramyl

N-Acetylmuramyi-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) 1 was shown (1) to be the minimal and essential s t ructure requi red for adjuvant activity o f bacterial cell wall peptidoglycans. Fur ther , MDP has been found to possess various biological activities, o ther than adjuvant activity, that are exer ted by bacterial cell wall peptidoglycans. Since MDP is such a potent immunomodula tor , efforts are being made to apply it to a clinical use. MDP should be carefully used, however, because it can induce some detr imental side effects; MDP induced adjuvant arthritis in rats (2), enhanced endotoxic shock in guinea pigs (3), caused pyrexia and leucopenia in rabbits (4-6), and induced the lethargy in cats, rabbits, and guinea pigs (7, 8). We repor t here ano the r kind of undesired effect o f MDP. In the course of study of antigenicity of MDP, we found that MDP could cause severe necrotic inflammation. Heat-killed tubercle bacilli incorpora ted into Freund-type wateroil emulsion injected into guinea pig footpads induced extensive necrosis in the footpads at the site o f tubercle bacilli injection when, 3 -5 wk later, MDP dissolved in Dulbecco's phosphate-buffered saline (PBS) was injected intracutaneously at the flank, and some animals died f rom generalized shock.