Some cellular and pathophysiological correlates of the inflammatory effects of a synthetic immunomodulatory agent, muramyl dipeptide (MDP)

Abstract

Acute, fully reversible paw edema was produced in mice after systemic administration of muramyl dipeptide (MDP, i.e. N-acetylmuramyl-L-alanyl-D-isoglutamine). Its stereoisomer N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP-D,D) was much less effective. The swelling of paws occurred very soon (1 h) after MDP injection, reached the maximum severity at an interval of 6 h and declined afterwards. While no substantial quantitative differences were found in the sensitivity of the various inbred strains of mice to edemagenic activity of MDP, athymic nude mice were completely resistant to the induction of edema. Formation of edema was blocked by silica, indomethacin (partially also by nordihydroguaiaretic acid), monoclonal antibodies against T-cells and their TH-subpopulation. It is suggested that the MDP-induced edema is a macrophage- and T-cell-dependent, prostaglandin- (and partially leukotriene)-mediated acute reaction associated with increased vascular permeability. Possible engagement of immune/inflammatory cytokines like IL-1 has been discussed. The data support the view that this type of edema is a consequence of changes in the activity of important cellular components of the immune system.