Species variability for toxicity of free and liposome-encapsulated muramyl peptides administered intravenously.

Muramyl dipeptide and muramyl tripeptide in free form or encapsulated within multilamellar liposomes were injected intravenously into (C57BL/6 X C3H)F1 mice and strain 2 guinea pigs to evaluate their potential acute, subacute, or chronic toxicity. Animals received either single or multiple (X 3, X 4, X 6, X 8) injections. A definite species variation was established with regard to the toxic nature of muramyl peptides. Mice failed to exhibit any changes of a clinical, biochemical, functional, or morphological nature in response to repeated intravenous administrations of high doses of muramyl peptide (free or in liposomes). In contrast, strain 2 guinea pigs were very sensitive to muramyl peptide, regardless of the dose or number of injections, or whether it was given in liposomes or as micelles (free form). Most guinea pigs exhibited vascular pathology reminiscent of the Schwartzman phenomenon. Further toxicity studies of muramyl peptides administered at relevant biological doses are recommended, as well as studies aimed at elucidating the reasons for the species variations.