Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids.

A total of 14 different N-acetylmuramyl-peptides or -amino acids with or without configurations inherent to bacterial cell wall peptidoglycans were synthesized and their pyrogenicities on intravenous injection into rabbits were tested. N-Acetylmuramyl-peptides, and especially N-acetylmuramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-lysine, which were previously shown to be adjuvant-active in both induction of delayed-type hypersensitivity and stimulation of increased serum antibody levels to ovalbumin in guinea pigs, exhibited distinct pyrogenicity at as low dose as 16 mug per rabbit. However, none of the adjuvant-inactive analogues or diastereomers of the above N-acetylmuramyl-dipeptide or related compounds caused any significant febrile response in rabbits, even at a dose of 250 mug per animal.