Differences in proinflammatory activity of several immunomodulatory derivatives of muramyl dipeptide (MDP) with special reference to the mechanism of the MDP effects.

Immunomodulatory agents, muramyl dipeptide (MDP) and several of its analogues, i.e. adamantylamide dipeptide, murametide, murabutide and their glucosaminylated derivatives, were tested for edemagenic activity in rats. Given systemically in aqueous solutions, only MDP and glucosaminylated MDP, at the dose of 3 mg/kg (s.c. or p.o.), were found to produce edematous swelling of the paws. Local (intra-pad) application of MDP was more effective than the systemic one. Supernatants of macrophages, in vitro cultured in presence of MDP, caused the swelling as well. The edema was of a transient nature. After reaching the maximum severity (about 6 h after injection of MDP solution or 1 h after macrophage supernatants), it was subsiding and disappeared completely within approximately 6 days after cessation of the treatment. It was found that this type of rat paw edema is probably a prostaglandin-dependent consequence of macrophage activation. Hypotheses on the involvement of immunoregulatory cytokines, and possible chemical structure-inflammatory activity relationships have been suggested.